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Small molecule mitochondrial uncouplers have gained traction for their potential therapeutic use against metabolic dysfunction-associated steatohepatitis (MASH). Herein, we report a novel imidazo[4,5-b]pyridine scaffold derived from iterative modifications of the potent uncoupler BAM15. Our structure-activity relationship (SAR) study demonstrated that this promising scaffold has a range of tolerated substitutions that allows for the modulation of uncoupling activity and in vivo pharmacokinetic properties. Specifically, compound SHS206 displayed an EC 50 of 830 nM in L6 myoblasts and, importantly, showed no cytotoxicity in vitro or adverse effects in mice up to 1000 mg/kg. SHS206 was administered orally at 100 and 300 mg/kg in a GAN mouse model of MASH and was observed to lower liver triglyceride levels while food intake, body weight, temperature, organ weights, and cholesterol levels remained unaltered. Together, these findings illuminate imidazo[4,5-b]pyridine as a promising scaffold for the future development of mitochondrial uncouplers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Webster L. Santos reports a relationship with Uncoupler Biosciences, Inc. that includes: board membership and equity or stocks. Kyle L. Hoehn reports a relationship with Uncoupler Biosciences, Inc. that includes: board membership and equity or stocks. 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 Elsevier Masson SAS. All rights reserved.)

Background: Community-based health check kiosks provide opportunities to improve the detection and long-term monitoring of hypertension. We describe the sociodemographic and cardiovascular characteristics of first-time and repeat users of these kiosks., Method: This was an observational study. Deidentified data collected from 430 SiSU Health consumer-facing health check stations in pharmacies across Australia between January 2018 and November 2020 were analyzed. Using a logistic regression, we identified factors associated with repeat checks in the overall cohort and in those with possible hypertension presented as adjusted odds ratios (aOR) and 95% CIs., Results: A total of 982 122 unique checks were conducted; 54% (n=530 139) of the health check users were female, and the average age of all users was 38.2 (SD 16.0) years. Of those that used the kiosks, 13% used them more than once. Overall, 22% met the definition of possible hypertension, 16% (n=136 345) had blood pressure (BP) ≥140/90 mm Hg, 4% (n=34 349) had BP >160/100 mm Hg, and 13% (121 282) reported taking BP medicines. In the adjusted analysis, first-time users who were aged 50 to 69 years (aOR 0.91 [95% CI 0.87-0.96]) or ≥70 years (aOR 0.68 [95% CI 0.62-0.74]) were less likely than young users (18-29 years) to return for a second health check. Those in very remote areas were 61% (aOR 0.39 [95% CI 0.19-0.72]), and smokers were 13% less likely to return (aOR 0.87 [95% CI 0.83-0.91]). People taking BP medications were more likely to return (aOR 1.16 [95% CI 1.09-1.22])., Conclusions: Community-based health checks may identify people with high BP and could provide an option for self-monitoring. Broader implementation is needed to increase the reach in rural areas and among the elderly population., Competing Interests: A.E. Schutte has received speaker honoraria from Omron and IEM™ and has conducted accuracy studies for Aktiia. M.P. Schlaich was supported by an National Health and Medical Research Council Research Fellowship and has received consulting fees, and/or travel and research support from Medtronic, Abbott, ReCor, Novartis, Servier, Pfizer, and BoehringerIngelheim. Australian Pharmaceutical Industries (API Ltd) maintains a minor shareholding in SiSU Health Group. API is now fully owned by Wesfarmers Ltd and forms part of the Wesfarmers Health division.

Individuals frequently update their beliefs and behaviours based on observation of others' experience. While often adaptive, social learning can contribute to the development of negative health expectations, leading to worsened health outcomes, a phenomenon known as the nocebo effect. This systematic review and meta-analysis examined: whether social learning is sufficient to induce the nocebo effect, how it compares to other forms of induction (classical conditioning and explicit instruction), and factors that influence these effects. The meta-analysis included twenty studies ( n = 1388). Social learning showed a medium-large effect size (Hedges' g = .74) relative to no treatment and a to small-medium effect ( g = .42) when compared to neutral modelling. The effect of social learning was similar in magnitude to classical conditioning but greater than explicit instruction with a small-medium effect ( g = .46). Face-to-face social modelling, longer exposure, higher proportions of female participants and models, and greater observer empathy led to stronger socially-induced nocebo effects. However, further research is essential as only a minority of studies measured important constructs like negative expectancies and state anxiety. Nonetheless, the study highlights social learning as a key pathway for nocebo effects, suggesting it as a target for interventions to reduce the substantial personal and societal burden caused by nocebo effects.

Purpose: The COVID-19 pandemic brought with it significant social, economic and health uncertainties. These were proposed to impact young people more compared to adults, leading adolescents to report more mental health problems during the pandemic. The current study examined whether differences in cognitive risk (tolerance of uncertainty) and protective (psychological flexibility) factors accounted for age-related differences in depression and anxiety., Methods: These associations were investigated in the COVID-19 Risks Across the Lifespan (CORAL) cohort (N = 2280, 11-89 years)., Results: The results showed that adolescents experienced greater intolerance of uncertainty and lower psychological flexibility compared to adults and older adults. Tolerance of uncertainty did not account for age-related differences in depression or anxiety. However, psychological flexibility conferred more protective advantage for anxiety in adults compared to adolescents., Conclusion: The observed age-related differences in risk and protective factors advance our understanding of developmental vulnerabilities to depression and anxiety. Implications for mental health interventions in the context of future pandemics are discussed., (© 2024. The Author(s).)

Purpose: Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known epidemiology of EB, highlight the disease's primary causative agents and their antimicrobial resistance spectrum. Materials and methods: A thorough literature search was conducted using Medline, EMBASE, JBI and PubMed to gather data on the microbial landscape of EB wounds. The focus was on identifying the most common bacteria associated with EB infections and assessing their antimicrobial resistance profiles. Results: The analysis revealed that Staphylococcus aureus is the most frequently identified bacterium in EB wounds, with a notable prevalence of methicillin-resistant strains (MRSA). Specific studies on mupirocin resistance further indicated rising rates of mupirocin-resistant Staphylococcus aureus , with one study reporting rates as high as 16.07%. Additionally, high resistance to other antibiotics, such as levofloxacin and trimethoprim/sulfamethoxazole, was observed in MRSA isolates. Conclusions: The findings highlight the critical need for regular resistance surveillance and the prudent use of mupirocin to manage infections effectively in EB. The multi-drug resistant nature of pathogens in EB presents a significant challenge in treatment, highlighting the importance of antimicrobial stewardship. Ultimately, given the sparse literature and the rarity of large-scale studies, further longitudinal research on the antimicrobial resistance profile of bacteria isolated from EB wounds is essential.

Background: Remote blood pressure monitoring refers to an organized framework that either allows clinicians to review home-based blood pressure readings and institute management, or provide participants with clear instructions for contacting care teams when blood pressure readings are out of prespecified targets. With widespread uptake of telemonitoring and mobile health in recent years, such models of care have been increasingly described in the literature., Objectives: This study aimed to review remote blood pressure monitoring in pregnant and postpartum women who are at high-risk for or have an established diagnosis of hypertensive disorders of pregnancy, and its effect on maternal and fetal outcomes, healthcare utilization and psychosocial outcomes., Search Strategy: PubMed, Medline, Embase, Cochrane Library, Web of Science and CINAHL databases were searched electronically in June 2024 to their inception., Study Selection Criteria: Included studies compared remote blood pressure monitoring with standard care. Remote blood pressure monitoring was pre-defined as any framework for measuring blood pressure remotely in pregnancy, with organized review by clinicians. Published full-text and study abstracts describing randomized controlled trials and observational studies were included. The study population was pregnant women at high-risk for developing pre-eclampsia or postpartum (<6 weeks) women with an established diagnosis of a hypertensive disorder of pregnancy. Remote blood pressure monitoring undertaken in the antenatal and postnatal periods were analyzed separately., Data Collection and Analysis: This systematic review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement. Screening of records and data extraction were independently performed. Data were extracted and analyzed using Review Manager software (version 5.4; Cochrane Collaboration, Copenhagen, Denmark). Risk of bias and quality assessment was performed independently using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) assessment tool and the Cochrane Risk of Bias 2 (RoB2) tool., Main Results: A total of 18 studies with 28 094 patients were included. Antenatal remote blood pressure monitoring reduces antenatal outpatient visits, antenatal hospital admissions for any cause, and antenatal hospital admissions specifically for hypertension. Importantly, there was no increase in adverse maternal and fetal outcomes, including the likelihood of cesarean section deliveries or induction of labor due to hypertension, composite maternal outcome, growth restriction, neonatal intensive care unit admissions, gestational age at delivery and the composite fetal outcome. Psychosocial outcomes were also not significantly different between the remote blood pressure monitoring and usual care groups. Postpartum remote blood pressure monitoring in women with an established hypertensive disorder of pregnancy led to greater compliance with blood pressure follow-up within 10 days, with no increase in unscheduled hypertension-related presentations, postpartum readmissions or outpatient antihypertensive prescription., Conclusions: Utilizing a model of remote blood pressure monitoring which incorporates organized review and management by clinicians, may reduce antenatal outpatient visits and admissions, without increasing adverse fetal and maternal outcomes, in pregnant women who require frequent monitoring of their blood pressure. In postpartum women with a hypertensive disorder of pregnancy, remote blood pressure monitoring can improve guideline recommended follow-up within 10 days. However, the meta-analysis was hampered by study heterogeneity and a paucity of high-quality evidence. Further randomized controlled trials are needed to confirm the findings of this review and provide recommendations., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Parent-Child Interaction Therapy-Toddler (PCIT-T) is an attachment-informed intervention model designed to meet the specific developmental needs of toddlers aged 12-24 months presenting with challenging behaviors., Methods: This study used a randomized controlled design to evaluate outcomes of PCIT-T for children aged 14-24 months with disruptive behaviors. Ninety toddlers with parent-reported disruptive behavior were randomly allocated to PCIT-T (intervention), an active control condition (Circle of Security- Parenting™; COS-P), or a non-treatment control condition (wait-list; WL). Outcomes were assessed at baseline (Time 1), post treatment/post waitlist (Time 2) and 4-month follow-up (Time 3)., Results: At follow-up, the PCIT-T group displayed the highest levels of parenting sensitivity and positive parental verbalizations, and the lowest levels of negative child-directed verbalizations and non-attuned mind-minded statements. Of the three groups, the PCIT-T group showed the greatest degree of change on these variables, followed by the COS-P group and then the non-treated controls. The PCIT-T group were also the only group to show significant within-group improvements in sensitivity, self-reported parental reflectiveness, empathy and emotional understanding, parent-reported child social competence, child internalizing problems, and general behavior issues. Significant reductions in parental stress, child externalizing behaviors and parenting behaviors were seen for both the PCIT-T and COS-P groups., Conclusions: Delivered in the early intervention period of toddlerhood, Parent-Child Interaction Therapy-Toddler has the potential to bring about significant changes for children presenting with early onset behavioral issues., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), 12,618,001,554,257. Registered 24 September 2018 - retrospectively registered, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001554257 ., Competing Interests: Declarations. Ethics approval and consent to participate: The project had full ethical clearance from the South Western Sydney Local Health District Human Research Ethics Committee (SWSLHD HREC); project number HREC/18/LPOOL/72. All participating parents gave written informed consent prior to participation, for themselves and for their child. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Abstract: The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and molecular based techniques. Data contained in quarterly reports are restricted to a description of case numbers of IMD by jurisdiction and serogroup, where known and expanded in 2024 to include antimicrobial resistance data for ceftriaxone, penicillin, ciprofloxacin and rifampicin. A full analysis of laboratory confirmations of IMD in each calendar year is contained in the AMSP annual reports., (© Commonwealth of Australia CC BY-NC-ND.)

Abstract: The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and molecular based techniques. Data contained in quarterly reports are restricted to a description of case numbers of IMD by jurisdiction and serogroup, where known and expanded in 2024 to include antimicrobial resistance data for ceftriaxone, penicillin, ciprofloxacin and rifampicin. A full analysis of laboratory confirmations of IMD in each calendar year is contained in the AMSP annual reports., (© Commonwealth of Australia CC BY-NC-ND.)

The increase in wildfires and bushfires due to climate change means that more people, including pregnant women and their fetuses will be exposed to landscape fire smoke. Although there is evidence to suggest that pregnancy landscape fire exposure is associated with lower birth weight, preterm birth and pregnancy loss, there is a lack of information on many other perinatal outcomes, as well as information on subsequent respiratory outcomes in children. Furthermore, due to the generally short term (hours/days) and intermittent nature of landscape fire smoke exposure, the knowledge to date has largely relied on natural experiments and ecological studies which can be subject to misclassification of exposure and a lack of precision. On the other hand, general urban outdoor air pollution exposure during pregnancy and subsequent perinatal and respiratory effects has been well studied. In particular, as air exposure modelling has improved so have the adaptations of methods to analyze the effects of air pollution exposure during pregnancy enabling critical windows of exposure to be identified. In this narrative review we summarize the current state of knowledge about the perinatal and respiratory effects of pregnancy landscape fire and particulate matter <2.5 μm in diameter (PM 2.5 ) air pollution exposure, including a comment on analysis methods to date, and an assessment of how methodologies used in general air pollution research in relation to pregnancy exposure can be further harnessed for landscape fire smoke exposure pregnancy research., 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 Ltd.. All rights reserved.)

Introduction: Routine collection of patient-reported outcome measures (PROMs) has the potential to inform and improve cancer care. It is now feasible for patients to complete PROMs electronically (ePROMs) providing information about their current levels of symptoms, side effects of treatment and other concerns. PROM scores can be tracked over time allowing more timely identification of problems and more appropriate intervention. Studies have reported clear benefits in patient-clinician communication when PROMs are used and trials in the USA and France found patients randomised to complete regular ePROMs reported better health-related quality of life, had fewer unplanned hospital visits and, importantly, significantly better survival than those randomised to usual care. However, information about the effects on health outcomes and, particularly, the cost-effectiveness of incorporating this information into practice is limited., Methods and Analysis: PROMISE (Patient Reported Outcome Measures in cancer care: a hybrid effectiveness-Implementation trial to optimise Symptom control and health service Experience) is a multicentre, randomised hybrid effectiveness/implementation trial to evaluate the clinical and cost-effectiveness of using ePROMs in routine cancer care to improve patient outcomes. Participants (target sample=572; randomised 1:1 to intervention and control) are adults aged 18 years or older diagnosed with a solid cancer and starting treatment at one of the four study hospitals. The primary outcomes are unplanned hospital presentations and physical/functional well-being at 6 months. We hypothesise that, compared with usual care, patients randomised to use an ePROM tool will have fewer unplanned hospital presentations, report better health-related quality of life and greater satisfaction with their care and that the ePROM tool will be cost-effective. We will also assess implementation and process outcomes consistent with the RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) Framework., Ethics and Dissemination: This trial has been approved by the Metro South Human Research Ethics Committee (HREC/2020/QMS/67441). Participants provide written informed consent, including consent for record linkage, prior to completing the baseline questionnaire. Study results will be disseminated via peer-reviewed journals and presentations at scientific conferences and clinical meetings., Trial Registration Number: ACTRN12620001290987., Competing Interests: Competing interests: PMW has received a speaker’s fee from AstraZeneca (December, 2021). ME and DW were part of the Metro North Health team that developed AboutMe and BB and LRW were part of the PAH team that developed My Health My Way but neither tool has been commercialised and none of the authors have any financial interests in the tools. RL has received grant funding from MSD for an unrelated study and sits on Advisory Boards for/has received honoraria and travel funding from MSD, L’Oreal and Sanofi. BB has been a member of the Metro South Human Research Ethics Committee since 2018 but was not involved in the review of this study., (© 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.)

Intervention: Health4Life: a school-based eHealth intervention targeting multiple health behaviour change (MHBC)., Research Question: Does Health4Life impact secondary outcomes of self-reported intentions regarding six lifestyle behaviours in adolescents (alcohol use, tobacco smoking, screentime, physical activity, discretionary beverage consumption, and sleep)?, Methods: We implemented a cluster randomized controlled trial within secondary schools across three Australian states. Schools were randomly assigned (1:1) to receive either the Health4Life intervention, which consisted of a six-module, web-based program and accompanying smartphone app, or an active control (standard health education). Randomization was stratified by site and school gender composition (using Blockrand in R). All students aged 11-13 years who attended the participating schools and were fluent in English were eligible. Students completed self-report questionnaires at baseline, post-intervention, 12 months, and 24 months. Outcomes were intentions to try alcohol, try tobacco, reduce screentime, engage in physical activity on most or all days, swap discretionary beverages for water, and meet sleep guidelines. Mixed effects models estimated between-group differences in the outcomes over 24 months., Results: Immediately post-intervention, Health4Life significantly reduced intentions to try alcohol and tobacco and increased intentions for longer sleep and reduced screentime compared to control. Intervention effects on screentime intentions persisted at 12 months but not at 24 months. No lasting effects were observed on intentions for physical activity or discretionary beverage consumption., Conclusion: Health4Life shows promise in influencing adolescent intentions across various MHBC areas, especially immediately after intervention. However, further investigation is needed to sustain these intention changes beyond short term to facilitate behaviour change., Competing Interests: Declarations Ethics approval The Health4Life trial had ethical approval from the Human Research Ethics Committees of the University of Sydney (2018/882), Curtin University (HRE2019-0083), the University of Queensland (2019000037), and relevant school sector ethics committees. Consent to participate Participation required active student consent and either passive (opt-out) or active (opt-in) parental consent, depending on school ethics board requirements. Conflict of interest MT and NCN are co-Directors of Climate Schools Pty Ltd and OurFutures Institute Ltd. There are no other potential conflicts of interest to report., (© 2024. The Author(s).)

Introduction and Hypothesis: Previous work has suggested that refractory detrusor overactivity (DO) was commonly associated with urinary tract infection (UTI), which can lead to inflammatory changes in the bladder. This study aimed to investigate the concentrations of urinary cytokines in a large sample of women with refractory detrusor overactivity (DO) and age matched controls., Methods: The urinary concentration of 27 cytokines in 140 women (95 with refractory DO and 45 age matched controls (women without urge incontinence)) was determined using the Human Cytokine 27-plex Assay. Cytokine concentrations were correlated with a "UTI score", the presence or absence of bacteriuria or pyuria on the day of sample collection and a previous history of UTI., Results: Pro-inflammatory cytokines were increased in refractory DO women compared to the controls. In women with refractory DO, the UTI score significantly correlated with urinary cytokine concentrations in 15 of the 22 cytokines detected. A previous history of UTI did not affect urinary cytokine concentrations in refractory DO women with no current UTI. Increasing pyuria was associated with increasing concentrations of urinary cytokines., Conclusion: Careful comparison of cytokine concentrations in women with refractory DO versus age matched controls has shown that changes in pro-inflammatory cytokines are related to the UTI disease burden, suggesting that an underlying inflammatory response, together with UTI, may be an aetiological contributor to the development of refractory DO., Competing Interests: Declarations Ethical Approval All participants provided written informed consent and the protocol was approved by the Ethics review committee (HREC18/G/219 South East Sydney Local Health District). Conflict of Interest The authors declare no conflict of interest., (© 2024. The International Urogynecological Association.)

The promise of urinary extracellular vesicles (uEVs) in biomarker discovery is emerging. However, the characteristics and compositions of different uEV subpopulations across normal physiological and pathological states require rigorous explication. We recently reported proteomic signatures of small (s)-uEVs (<200 nm membranous nanoparticles) and described putative biomarkers corresponding to the diagnosis, tumour burden and recurrence of the lethal adult primary brain tumour, glioblastoma. Here, we comprehensively characterise uEV populations with significantly different mean and mode particle sizes obtained by differential centrifugation at 100,000 ×  g (100K-uEVs; smaller) and 17,000 ×  g (17K-uEVs; larger) using Fourier-transform infrared spectroscopy and quantitative data-independent acquisition mass spectrometry. We show distinct differences in protein and lipid content, prominent protein secondary structures, and proteome distributions between uEV populations that can distinguish glioblastoma patients from healthy controls and correspond to clinically relevant tumour changes (i.e., recurrence and treatment resistance). Among the key findings is a putative seven-protein biomarker panel associated with 17K-uEVs that could distinguish all glioblastoma patients from healthy controls and accurately classify 98.2% of glioblastoma samples. These novel, significant findings demonstrate that both uEV populations offer individual and combined biomarker potential. Further research is warranted to elucidate the complete diagnostic, prognostic, and predictive capabilities of often-neglected 17K-uEV populations., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Promoting vaccine acceptance and demand is an essential, yet often underrecognized component of ensuring that everyone has access to the full benefits of immunization. Convened by the Sabin Vaccine Institute, the Vaccination Acceptance Research Network (VARN) is a global network of multidisciplinary stakeholders driving strengthened vaccination acceptance, demand, and delivery. VARN works to advance and apply social and behavioral science insights, research, and expertise to the challenges and opportunities facing vaccination decision-makers. The second annual VARN conference, When Communities Lead, Global Immunization Succeeds, was held June 13-15, 2023, in Bangkok, Thailand. VARN2023 provided a space for the exploration and dissemination of a growing body of evidence, knowledge, and practice for driving action across the vaccination acceptance, demand, and delivery ecosystem. VARN2023 was co-convened by Sabin and UNICEF and co-sponsored by Gavi, the Vaccine Alliance. VARN2023 brought together 231 global, regional, national, sub-national, and community-level representatives from 47 countries. The conference provided a forum to share learnings and solutions from work conducted across 40+ countries. This article is a synthesis of evidence-based insights from the VARN2023 Conference within four key recommendations: (1) Make vaccine equity and inclusion central to programming to improve vaccine confidence, demand, and delivery; (2) Prioritize communities in immunization service delivery through people-centered approaches and tools that amplify community needs to policymakers, build trust, and combat misinformation; (3) Encourage innovative community-centric solutions for improved routine immunization coverage; and (4) Strengthen vaccination across the life course through building vaccine demand, service integration, and improving the immunization service experience. Insights from VARN can be applied to positively impact vaccination acceptance, demand, and uptake around the world., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rupali Limaye reports a relationship with Sabin Vaccine Institute that includes: funding grants. Eve Dube reports a relationship with Sabin Vaccine Institute that includes: travel reimbursement. Holly Seale reports a relationship with Sabin Vaccine Institute that includes: travel reimbursement. Rubina Qasim reports a relationship with Sabin Vaccine Institute that includes: travel reimbursement. 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 Ltd.. All rights reserved.)

The mechanisms by which oncogenic mutations and anatomical locations work together to influence the immune environment within tumors are not well understood. In this issue of Immunity, Ross et al. show that H3.3K27M diffuse midline gliomas (DMGs) are enriched with disease-associated myeloid cells (DAMs). Myeloid-targeted strategies reprogram DAMs to a homeostatic state, reduce myeloid infiltration into tumors, and prolong survival., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Both depression and respiratory disease are common today in young populations. However, little is known about the relationship between them., Aims: This study aims to explore the association between depression in childhood to early adulthood and respiratory health outcomes in early adulthood, and the potential underlying mechanisms., Method: A prospective study was conducted based on the Swedish BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi [Children, Allergy, Milieu, Stockholm, Epidemiology]) birth cohort ( n = 4089). We identified clinically diagnosed depression through the dispensation of antidepressants, using national register data confirmed by self-reported diagnosis. At the 24-year follow-up, respiratory health was assessed via questionnaires and clinical evaluation. Metabolic and inflammatory profiles were analysed to explore potential mechanisms., Results: Among the 2994 participants who provided study data, 403 (13.5%) had depression at any time point from around age 10 to 25 years. Depression was associated with higher risks of any chronic bronchitis symptoms (odds ratio = 1.58, 95% CI 1.21-2.06) and respiratory symptoms (odds ratio = 1.41, 95% CI 1.11-1.80) in early adulthood, independent of body mass index (BMI) and smoking status. Compared to individuals without depression, those with depression had a higher fat mass index (FMI (β = 0.48, 95% CI 0.22-0.74)) and increased blood levels of fibroblast growth factor 21 and Interleukin-6 in early adulthood. These markers together with FMI were found to partly mediate the association between depression and respiratory symptoms (total mediation proportion: 19.8 and 15.4%, respectively, P < 0.01)., Conclusions: Depression in childhood to early adulthood was associated with an increased risk of respiratory ill-health in early adulthood, independently of smoking. Metabolic and inflammatory dysregulations may underlie this link.

Control of the morphology of polymer systems is achieved through reversible-deactivation radical polymerization techniques such as Reversible Addition-Fragmentation chain Transfer (RAFT). Advanced RAFT techniques offer much more than just "living" polymerization - the RAFT toolkit now enables morphological control of polymer systems across many decades of length-scale. Morphological control is explored at the molecular-level in the context of syntheses where individual monomer unit insertion provides sequence-defined polymers (single unit monomer insertion, SUMI). By being able to define polymer architectures, the synthesis of bespoke shapes and sizes of nanostructures becomes possible by leveraging self-assembly (polymerization induced self-assembly, PISA). Finally, it is seen that macroscopic materials can be produced with nanoscale detail, based on phase-separated nanostructures (polymerization induced microphase separation, PIMS) and microscale detail based on 3D-printing technologies. RAFT control of morphology is seen to cross from molecular level to additive manufacturing length-scales, with complete morphological control over all length-scales., (© 2024 Wiley‐VCH GmbH.)

Background: The reference change value (RCV) is calculated by combining the within-subject biological variation (CVI) and local analytical variation (CVA). These calculations do not account for the variation seen in preanalytical conditions in routine practice or CVI in patients presenting for treatment. As a result, the RCVs may not reflect routine practice or align with clinicians' experiences. We propose a novel RCV approach based on routine patient data that is potentially more clinically relevant., Methods: This study used the refineR algorithm to determine RCVs using serial patient data extracted from a local Laboratory Information System (LIS). The model was applied to biomarkers with a range of result ratio distributions varying from normal to log-normal. Results were compared against conventional formula-based RCVs using CVI estimates from a state-of-the-art biological variation study. Monte Carlo simulations were also used to validate the LIS data approach., Results: The RCVs estimated from LIS data were: 11-deoxycortisol (men): -70%/+196%, 17-hydroxyprogesterone (men): -49%/+100%, albumin: -10%/+11%, androstenedione (men): -47%/+96%, cortisol (men): -54%/+51%, cortisone (men): -32%/+51%, creatinine: -16%/+14%, phosphate (women): -23%/+29%, phosphate (men): -27%/+29%, testosterone (men): -38%/+60%. The formula-based RCV estimates showed similar but slightly lower results, and the Monte Carlo simulations confirmed the applicability of the new approach., Conclusions: RCVs may be estimated from patient results without prior assumptions about the shape of the ratios between serial results. Laboratories can determine RCVs based on local practice and population., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: External causes of death, such as accidents, substance use, and suicide, contribute substantially to mortality during adolescence and early adulthood and show marked sex differences. Individuals born preterm are at increased risk of mental disorders, and impaired cognitive and executive functions, potentially increasing their vulnerability to death from external causes. We investigated sex-specific associations between gestational age at birth and mortality from external causes during late adolescence and early adulthood., Methods: Individual level data from national health registries in Denmark (1978-2001), Finland (1987-2003), Norway (1967-2002), and Sweden (1974-2001) were linked to form nationwide cohorts. In total, 6,924,697 participants were followed from age 15 years to a maximum of 50 years in 2016-2018. Gestational age was categorized as "very/moderately preterm" (23-33 weeks), "late preterm" (34-36 weeks), "early term" (37-38 weeks), "full term" (39-41 weeks), and "post term" (42-44 weeks). Outcomes were mortality from external causes overall and from the largest subgroups transport accidents, suicide, and drugs or alcohol. We estimated sex-specific hazard ratios (HRs), with full term as the reference, and pooled each country's estimates in meta-analyses., Results: Across gestational ages mortality was higher for males than females. Individuals born very/moderately preterm had higher mortality from external causes, with HRs 1.11 (95% confidence interval [CI] 0.99-1.24) for males and 1.55 (95% CI 1.28-1.88) for females. Corresponding estimates for late preterm born were 1.11 (95% CI 1.04-1.18) and 1.15 (95% CI 1.02-1.29), respectively. Those born very/moderately preterm had higher mortality from transport accidents, but precision was low. For females, suicide mortality was higher following very/moderately preterm birth (HR 1.76, 95% CI 1.34-2.32), but not for males. Mortality from drugs or alcohol was higher in very/moderately and late preterm born males (HRs 1.23 [95% CI 0.99-1.53] and 1.29 [95% CI 1.16-1.45], respectively) and females (HRs 1.53 [95% CI 0.97-2.41] and 1.35 [95% CI 1.07-1.71], respectively, with some heterogeneity across countries)., Conclusions: Mortality from external causes overall was higher in preterm than full term born among both males and females. A clear sex difference was seen for suicide, where preterm birth was a risk factor in females, but not in males., (© 2024. The Author(s).)

With large wildfires becoming more frequent 1,2 , we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 3,4 2019-2020 Australian megafires burnt more than 10 million hectares 5 , prompting major investment in biodiversity monitoring. Collated data include responses of more than 2,000 taxa, providing an unparalleled opportunity to quantify how megafires affect biodiversity. We reveal that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas. Areas burnt at high severity, outside protected areas or under extreme drought also had larger effects. The effects included declines and increases after fire, with the largest responses in rainforests and by mammals. Our results implicate species interactions, dispersal and extent of in situ survival as mechanisms underlying fire responses. Building wildfire resilience into these ecosystems depends on reducing fire recurrence, including with rapid wildfire suppression in areas frequently burnt. Defending wet ecosystems, expanding protected areas and considering localized drought could also contribute. While these countermeasures can help mitigate the impacts of more frequent megafires, reversing anthropogenic climate change remains the urgent broad-scale solution., Competing Interests: Competing interests: The authors declare that some of them work for government agencies involved in forestry and implementing planned burns (Supplementary Table 8). The lead author declares that, despite the potential for government agencies to impose policy positions on staff communications (see ref. 51), scientific independence and integrity has been maintained throughout this project., (© 2024. The Author(s).)