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Background: Remission is the desired outcome following OIT as it allows individuals to discontinue treatment and eat the allergen freely. Early initiation of OIT in infants and toddlers has been embraced as an approach to increase the likelihood of remission. However, there is no high-quality evidence supporting younger age as an independent factor driving remission; available studies are limited by small samples of younger subjects and lack of adjustment for confounding covariates, particularly peanut-specific IgE (sIgE) levels which is closely correlated with age., Methods: This study examined relationships between peanut sIgE and age at baseline and remission, in children aged 1-10 who completed 18 months of OIT in the PPOIT-003 RCT (n = 162). Remission was defined as absence of clinical reactivity to peanut after 8 weeks of allergen avoidance/treatment discontinuation. Age and sIgE were examined as continuous variables in univariate and multivariate regression models., Results: Higher peanut sIgE was consistently predictive of lower likelihood of remission, independent of age. In contrast, there was no independent association between age and remission after adjusting for baseline sIgE (OR 0.94 [0.79-1.12], p = 0.5)., Conclusions: Findings do not support age as an independent predictor of remission following OIT. Additional studies examining safety and efficacy of OIT in infants and younger children are urgently needed, ahead of widespread adoption of early intervention., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome. Previous studies suggest that SUMOylation, a posttranslational modification consisting of conjugation of SUMO (Small ubiquitin-like modifier) to target proteins, was decreased in the hippocampus of AD patients and in animal model of AD compared with controls. This decrease in SUMOylation was correlated with increased Tau pathology and cognitive decline. Other studies have reported increased levels of SUMO in AD brains. The goal of our study was to evaluate whether SUMO conjugation modifies the neurodegenerative disease pathology associated with the aggregation-prone mutant TauP301L, in neurons and in glial cells., Methods: We used viral approaches to express mutant TauP301L and SUMO2 in the hippocampus of wild-type mice. We assessed Tau distribution by immunostaining and Tau aggregation by insolubility assays followed by western blotting. We assessed neuronal toxicity and performed cell count and shape descriptor analyses on astrocytes and microglial cells., Results: We found that mutant TauP301L, when expressed exclusively in neurons, is toxic not only to neurons but also to glial cells, and that SUMO2 counteracts TauP301L toxicity in neurons as well as in glia., Discussion: Our results uncover an endogenous neuroprotective mechanism, whereby SUMO2 conjugation reduces Tau neuropathology and protects against toxic effects of Tau in glial cells., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Orsini, Pascente, Martucci, Palacino, Fraser, Arancio and Fioriti.)

Background: Complex Regional Pain Syndrome type 1 (CRPS-1) is severely debilitating and painful disease that is difficult to treat., Objective: The objective was to evaluate the long-term residual disability of patients with CRPS-1 following parenteral neridronate treatment., Design: This is real-life retrospective observational study., Methods: Patients affected by CRPS-1 of the upper limb were treated with neridronate infusions (400 mg over 10 days) between February 2017 and December 2021 for whom clinical and demographic information was collected. From November 2022, patients treated ⩾1 year previously were recalled for clinical evaluation. A dedicated instrument (DASH questionnaire, Disabilities of the Arm, Shoulder and Hand) was employed to assess residual disability. Multivariate logistic regression analysis was used to investigate predictors of disability., Results: Forty-nine patients aged 61.1 ± 11.5 years and 73.5% female with CRPS-1 of the upper limb were included. Disease duration before treatment was 9.9 ± 8.0 weeks, and the mean length of follow-up was 4 years (47.7 ± 22.0 months). The disease had fully resolved in 46 patients (93.9%) for whom the diagnostic criteria were no longer recognized. According to the DASH score, 38 patients (77.6%) resulted free of functional limitations, whereas 11 patients (22.4%) were still suffering from disability. The DASH score was positively correlated with residual visual analogue scale (VAS; Spearman's Rho = 0.61; P  < .001). Predictors of residual disability were younger age (odds ratio [OR]: 0.77, 95% CI: 0.63-0.93; P  = .012) and delay between disease onset and treatment (OR: 1.45, 95% CI: 1.13-1.96; P  = .004)., Conclusions: In this real-life study, neridronate parenteral treatment provided a full recovery of CRPS-1 in over 3 quarters of patients, provided they are treated early., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: MV served as consultant for Abiogen. CC, FO, FZ, GC and RC have no conflicts of interest to declare., (© The Author(s) 2024.)

Introduction: Strong oral language and reading skills are important for child development. The response to intervention (RTI) framework supports schools to apply evidence-based practices and interventions to proactively meet the learning needs of all students and identify and support students at risk of learning difficulties. Getting it Right from the Start (GIRFTS) aims to implement a codesigned RTI framework in the first 2 years of formal schooling (foundation and grade 1) to improve oral language and reading skills. GIRFTS includes an implementation evaluation., Methods and Analysis: GIRFTS is a stepped-wedge cluster randomised trial conducted in Victoria, Australia, over 3 years. Clusters are primary schools. The intervention is to implement tiers 1 and 2 of the RTI framework into foundation and grade 1 according to RTI principles. The primary outcome is reading comprehension by the start of grade 2. Secondary outcomes include listening comprehension, word and non-word reading and phonological awareness. An implementation evaluation will also be conducted with the study to understand schools' RTI implementation process and enablers and barriers to implementation. Strategies used by schools to overcome implementation challenges will also be investigated., Ethics and Dissemination: This trial was approved by the Royal Children's Hospital Human Research Ethics Committee (HREC/58832/RCHM-2019). Investigators will communicate the results to stakeholders, collaborators and participating schools and teachers through presentations and publications., Trial Registration Numbers: ISRCTN91164066, ACTRN12622000146796., Competing Interests: Competing interests: PS is the Co-Director of the La Trobe University Science of Language and Reading (SOLAR) Lab. The short course that is part of the intervention described in this paper is delivered by the SOLAR Lab. PS does not receive any financial benefit from SOLAR Lab activities. There are no other competing interests 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.)

Mosaic variegated aneuploidy (MVA) is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies, and most patients present with intrauterine growth delay, microcephaly, and a broad spectrum of congenital abnormalities. We report a patient with a distinctive type of MVA discovered in bone marrow (BM) when she was 3-month-old due to neutropenia and hypocellular bone marrow. She was followed up for more than 20 years, and different trisomic cells were repeatedly discovered in different tissues, whereas her clinical picture has never been severe. The main sign remained intermittent neutropenia, not cyclic and often not too severe, occasionally with anemia and thrombocytopenia. Retromicrognathia was the only dysmorphic sign. Unlike other patients with MVA, the trisomies in all tissues involved almost invariably chromosomes 18 and 19. Therefore, the peculiarities of our patient were the clinical and the atypical cytogenetic pictures. Nevertheless, we looked for mutations in the seven causative genes of the known types of MVA, but the results were negative. Then, we analyzed the entire exome to find out other possible causing mutations, but also this attempt failed to discover a possible cause of this distinctive form of MVA., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Pediatric obesity has been described by the World Health Organization as 1 of the most serious public health challenges of the 21st century. Projections of increasing burdens of pediatric obesity and its related diseases on society highlight the need for urgent and substantial action. Many scientific and public debates about the prevention of childhood obesity are centered around simple dichotomies presenting a single-level solution. In contrast, efficient prevention programs should overcome these overly simplistic dichotomies and proceed in the early years of life within the family environment and the whole society, throughout one's lifetime. Food policies have the potential to counteract pediatric obesity by creating healthy food environments. However, the current food policies approach lacks monitoring indicators to assess short- and long-term impact, and is not well integrated into regional, national, and cross-cutting initiatives. Therefore, redesigning and rethinking food policy strategies and goals is an important opportunity to address childhood obesity, safeguard the planet, and contribute to economic and social prosperity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Childhood obesity has become a significant public health concern over the past 2 decades, posing multifactorial challenges, including modifiable factors like dietary habits, physical activity, screen time, and sleeping habits. Prevention efforts require a comprehensive approach comprising educational interventions, collaboration among multidisciplinary teams, and community engagement. Since schools play a central role in children's lives, they are the ideal setting for promoting healthy habits., Objective: The LIVELY (Multidimensional School-Based and Family-Involved Interventions to Promote a Healthy and Sustainable Lifestyle) study will assess the prevalence of overweight and obesity in primary school children and identify contributing factors within families. Additionally, it aims to implement and evaluate a multidimensional, multidisciplinary intervention to foster a sustainable and healthy lifestyle, ultimately working toward preventing obesity in school-aged children., Methods: During the school year, each class will be individually involved in a multidimensional educational intervention covering the topics of healthy, sustainable nutrition and lifestyle. Children will also participate in a multimedia lab where they will create an animated cartoon. The lectures will engage them through various methods, including direct instructions, games, and drawing activities, to stimulate and enhance their learning and involvement., Results: Data collection began in October 2023 and will last until the end of October 2024. A sample of 227 children from 14 classes was included in the study. The mean age was 8.9 (SD 1.2) years, and 48% (n=110) were males. Among the overall sample, 18.1% (n=41; 95% CI 13.7%-23.7%) were overweight, while 5.3% (n=12; 95% CI 3%-9%) had obesity. Males had a higher prevalence of obesity than females (9.1%, n=10 vs 1.7%, n=3, P=.03, respectively). Otherwise, the prevalence of central obesity was similar between the two (P=.329). Data analysis and the presentation of the complete results will be available after the end of 2024., Conclusions: The study could lead to the structuring of an educational intervention model in school settings aimed at preventing childhood obesity. Moreover, it could help raise awareness of childhood obesity and help prevent this public health issue., Trial Registration: ClinicalTrials.gov NCT05966051; https://clinicaltrials.gov/study/NCT05966051., International Registered Report Identifier (irrid): DERR1-10.2196/57509., (©Sara Basilico, Maria Vittoria Conti, Ilaria Ardoino, Chiara Breda, Federica Loperfido, Elena Klaic, Linda Spialtini, Andreana Foresta, Francesca Orsini, Maria Luisa Ojeda Fernandez, Stefano Conca Bonizzoni, Elisabetta Modena, Yasamin Tootoonchi Hamedani, Federica Villa, Hellas Cena, Marta Baviera, Carlotta Franchi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.10.2024.)

Background: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission)., Methods: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic)., Results: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001)., Conclusion: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

To explore serum levels of some bone turnover markers and the involvement of the Wnt signaling in CRPS-1. Query ID="Q1" Text="Please check and confirm whether the edit made to the article title is in order." We conducted an observational study on patients with early CRPS-1 recruited before any treatment. Clinical measures were assessed together with biochemical evaluation. Values of sclerostin, DKK1, CTX-I, and P1NP were compared with sex-age-matched healthy controls (HCs). We enrolled 34 patients diagnosed with CRPS-1 (mean age 59.3 ± 10.6 years, Male/Female 10/24), median disease duration = 2 weeks (IQR 1-5); median VAS score = 76 (IQR 68-80). Foot localization was slightly more frequent than hand localization (18/16). No statistically significant difference was found between CRPS-1 patients and HCs for CTX-I (0.3 ± 0.1 ng/ml vs 0.3 ± 0.1, p = 0.140), while mean serum values of P1NP were significantly higher in CRPS-1 patients compared to HCs (70.0 ± 38.8 ng/ml vs 50.1 ± 13.6, p = 0.005). Mean levels of sclerostin and DKK1 were lower in CRPS-1 patients vs HCs (sclerostin 28.4 ± 10.8 pmol/l vs 34.1 ± 11.6, p = 0.004; DKK1 12.9 ± 10.8 pmol/l vs 24.1 ± 11.9, p = 0.001). No statistically significant difference was found for all biochemical assessments in a subgroup of fracture-induced CRPS-1. No statistically significant differences were observed according to disease localization, disease duration, presence of hyperalgesia, allodynia, sudomotor alterations, and mild or moderate/severe swelling. No significant correlation emerged between sclerostin, DKK1 levels, baseline VAS score, or McGill Pain Questionnaire score. Bone involvement in early CRPS-1 does not seem to rely on increased osteoclast activity. Conversely, a serum marker of bone formation resulted increased. Both Sclerostin and DKK1 showed decreased values, probably suggesting a widespread osteocyte loss of function.Trial registration number: Eudract Number: 2014-001156-28., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: The Mediterranean Diet (MD) has been recognized for its benefits for human health and sustainability for the planet, but it has considered not easy to reproduce in other populations. The United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair on Health Education and Sustainable Development is fostering a research project (Planeterranea), aiming to identify a healthy dietary pattern based on local foods with the same MD features. The aim of our study is to develop a MD-based food pyramid for Asian populations., Methods: Asia was stratified into six areas according to pedo-climatic conditions. For each region a comprehensive scoping review of local crops and typical foods was conducted on several databases such as the US Department of Agriculture (USDA)'s database, the Food and Agriculture Organization of the United Nations (FAO) website, and PubMed, focusing on both plant-based and animal-based foods. Narrative review was then conducted on the identified foods to determine their nutritional composition and planetary health impact. Finally, the collected information was used to build up the Asian food pyramid with details for each respective region., Results: We proposed a food pyramid for Asian countries, guaranteeing the same nutritional intake and health benefits as MD, by considering dietary habits and typical foods of this population. From the bottom to the top, Asian fruits and vegetables present similar nutritional profile as those in MD. Whole grains (barley) may represent valid alternative to white rice. Sesame oil represents a source of unsaturated fats and an alternative to olive oil. Legumes (soybean), edible insects, mushrooms and algae, guarantee an adequate intake of plant-based proteins with a complete amino-acid profile and a low environmental impact with respect to animal-based ones., Conclusions: This work is a new insight of healthy and sustainable local food system based on MD principles for the Asian population., (© 2024. The Author(s).)

The study of the relationship between Daylight Saving Time (DST) and road safety has yielded contrasting results, most likely in relation to the inability of crash-database approaches to unravel positive (ambient lighting-related) and negative (circadian/sleep-related) effects, and to significant geographical differences in lighting-related effects. The aim of this study was to investigate the effects of DST on driving fatigue, as measured by driving-based, physiological and subjective indicators obtained from a driving simulator experiment. Thirty-seven participants (73 % males, 23 ± 2 years) completed a series of 50-min trials in a monotonous highway environment: Trial 1 was in the week prior to the Spring DST transition, Trial 2 in the following week, and Trial 3 in the fourth week after the transition. Thirteen participants returned for Trial 4, in the week prior to the Autumn switch to civil time, and Trial 5 in the following week. Significant adverse effects of DST on vehicle lateral control and eyelid closure were documented in Trial 2 and Trial 3 compared to Trial 1, with no statistical differences between Trials 2 and 3. Further worsening in vehicle lateral control was documented in Trials 4 and 5. Eyelid closure worsened up to Trial 4, and improved in Trial 5. Participants were unaware of their worsening performance based on subjective indicators. In conclusion, DST has a detrimental impact on driving fatigue during the whole time during which it is in place. Such an impact is comparable, for example, to that associated with driving with a blood alcohol concentration of 0.5 g/L., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Homicide by drowning in adults is rare. Usually, marks of violence are found on both the victim and the perpetrator, unless the victim was under the influence of alcohol, drugs, or was unexpectedly forced or dragged into the water. Indeed, many cases of drowning in adults are believed to be accidental, but they may be the result of drunken fights or attempts to make the death appear ac-cidental. In order to define the manner of death, cooperation between the forensic pathologist and the investigators is mandatory. Indeed, the autopsy is important to distinguish homicide by drowning from other kinds of drowning. The purpose of this study is to highlight the features of homicide by drowning., Materials and Methods: Literature search was conducted using PubMed databases, using the following keywords: "(homicide) and (drowning)". 3 articles were included in the systematic review, in addition to 3 cases observed in our institute., Conclusions: Both external examination and autopsy findings and the results of the investigation are essential to differentiate a homicide by drowning from accidental ones. The low specificity and variability of external and internal findings, the possibility of atypical asphyctic and nonasphyctic pathophysiological mechanisms, whose nature is not detectable at postmortem examinations, makes the diagnosis of cause of death difficult and often based on exclusion criteria only. In complex cases only using a strict forensic method allows to use the essential tools to identify the real manner of death.

Neurologic manifestations are an immediate consequence of SARS-CoV-2 infection, the etiologic agent of COVID-19, which, however, may also trigger long-term neurological effects. Notably, COVID-19 patients with neurological symptoms show elevated levels of biomarkers associated with brain injury, including Tau proteins linked to Alzheimer's pathology. Studies in brain organoids revealed that SARS-CoV-2 alters the phosphorylation and distribution of Tau in infected neurons, but the mechanisms are currently unknown. We hypothesize that these pathological changes are due to the recruitment of Tau into stress granules (SGs) operated by the nucleocapsid protein (NCAP) of SARS-CoV-2. To test this hypothesis, we investigated whether NCAP interacts with Tau and localizes to SGs in hippocampal neurons in vitro and in vivo. Mechanistically, we tested whether SUMOylation, a posttranslational modification of NCAP and Tau, modulates their distribution in SGs and their pathological interaction. We found that NCAP and Tau colocalize and physically interact. We also found that NCAP induces hyperphosphorylation of Tau and causes cognitive impairment in mice infected with NCAP in their hippocampus. Finally, we found that SUMOylation modulates NCAP SG formation in vitro and cognitive performance in infected mice. Our data demonstrate that NCAP induces Tau pathological changes both in vitro and in vivo. Moreover, we demonstrate that SUMO2 ameliorates NCAP-induced Tau pathology, highlighting the importance of the SUMOylation pathway as a target of intervention against neurotoxic insults, such as Tau oligomers and viral infection.

Purpose: Spontaneous muscle hematomas (SMH) are frequently seen in the Emergency Department (ED), particularly as a complication of anticoagulation treatments. To date, there are no standard guidelines for the management of this condition in the ED. This work aims to identify clinical-radiological parameters of SMH at risk of poor outcomes., Method: This is a retrospective, observational cohort study conducted in an urban teaching hospital from 2016 to 2019. A multivariate logistic regression analysis was performed to identify parameters independently associated with an adverse outcome defined as the need for treatment (blood products, TAE, surgery) or hospitalization. The parameters analyzed were hematoma size, anticoagulation therapy, age, and the Charlson Comorbidity Index (CCI). ROC analysis was performed to identify the best cut-off hematoma size value to predict poor outcomes., Results: Our study enrolled 231 patients aged between 18 and 96 years, with a mean age of 67 years. In our population, 125 patients (54.1 % %) were on anticoagulant therapy. Multivariate analysis showed that an SMH diameter > 5.5 cm was independently associated with poor outcome ((odds Ratio [95 % CI] 4,009 [1,786-9,001], p 0.001). Among clinical parameters, only advanced age was proved to be an independent predictor of adverse outcomes (odds Ratio [95 % CI] 1,035 [1,003-1,069], p = 0.033) CONCLUSIONS: Our data suggest that an SMH diameter greater than 5.5 cm on a CT scan and advanced age are predictors of poor outcomes. Surprisingly, anticoagulant therapy seems to play a minor role in the outcome of SMHs., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults., Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206., Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination., Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease., Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors., Competing Interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/and declare: the trial is financially supported by the Foundations listed in the Funding section. Authors disclose funding support over the past 36 months: National Health and Medical Research Council (NHMRC) Ideas Grant (NM), Investigator Grant (NC); Melbourne Children's Clinician-Scientist Fellowship Grant (KPP); Institutional support for research grants, presentations, meeting attendance and participation on Scientific Advisory Boards related to pertussis, RSV, pneumococcal, meningococcal and COVID-19 diseases from GlaxoSmithKline, Merck Sharpe & Dohme, Pfizer, Clover Biopharmaceuticals and Resvinet Foundation (PCR); grant support from Sanofi, MSD & CEPI for COVID-19 vaccine/drug research (JC). PCR has participated on Astra Zeneca COVID-19 Scientific Advisory Board and has a bacteriotherapy patent pending. JC participates on Latin American data safety monitoring/advisory boards for mRNA-1273 (Modern/Zodiac), RSV maternal vaccine (Pfizer), Qdenga vaccine (Takeda), Nirmatrelvir/Ritonavir-Paxlovid (Pfizer) and recently presented to Foro Latinoamericano para Asesores Médicos en Vacunas (Pfizer). NW has participated in the Covalia COVID-19 DNA vaccine trial in an advisory/data safety monitoring board capacity. KG is a member of the Royal Children's Hospital (RCH) Human Research Ethics Committee (the primary ethics committee providing approval for the BRACE trial) and Director of Research Operations at RCH; she abstained from all discussion, voting, approval and review related to the BRACE trial., (© 2024 The Author(s).)

Background: The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care., Objectives: This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects., Methods: The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models., Results: A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects., Conclusions: Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Urban agriculture (UA) activities are increasing in popularity and importance due to greater food demands and reductions in agricultural land, also advocating for greater local food supply and security as well as the social and community cohesion perspective. This activity also has the potential to enhance the circularity of urban flows, repurposing nutrients from waste sources, increasing their self-sufficiency, reducing nutrient loss into the environment, and avoiding environmental cost of nutrient extraction and synthetization. The present work is aimed at defining recovery technologies outlined in the literature to obtain relevant nutrients such as N and P from waste sources in urban areas. Through literature research tools, the waste sources were defined, differentiating two main groups: (1) food, organic, biowaste and (2) wastewater. Up to 7 recovery strategies were identified for food, organic, and biowaste sources, while 11 strategies were defined for wastewater, mainly focusing on the recovery of N and P, which are applicable in UA in different forms. The potential of the recovered nutrients to cover existing and prospective UA sites was further assessed for the metropolitan area of Barcelona. Nutrient recovery from current composting and anaerobic digestion of urban sourced organic matter obtained each year in the area as well as the composting of wastewater sludge, struvite precipitation and ion exchange in wastewater effluent generated yearly in existing WWTPs were assessed. The results show that the requirements for the current and prospective UA in the area can be met 2.7 to 380.2 times for P and 1.7 to 117.5 times for N depending on the recovery strategy. While the present results are promising, current perceptions, legislation and the implementation and production costs compared to existing markets do not facilitate the application of nutrient recovery strategies, although a change is expected in the near future., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Urban design is currently promoting the inclusion of plants in buildings. However, plants emit biogenic volatile organic compounds (BVOCs), which alone or in combination with other airborne molecules such as CO 2 , may result in a general increase in tropospheric pollution. Many studies have documented the effects of biotic and abiotic factors on plant BVOC responses, but few have assessed the contribution of typical CO 2 levels found in indoor work and meeting spaces. To answer this question, we monitored CO 2 and constitutive (MT-limonene) and induced (LOX-cis-3-hexenal) BVOC emissions of a fully developed tomato crop grown hydroponically inside an integrated rooftop greenhouse (i-RTG) in a Mediterranean climate. Two distinctive CO 2 assays were performed at the level of the i-RTG by supplying or not CO 2 . The impact of CO 2 on plant physiological emittance was then assessed, and the resulting BVOC rates were compared with reference to EU-LCI values. MT-limonene was ubiquitous among the assays and the most abundant, while LOX-cis-3-hexenal was detected only under controlled CO 2 management. The highest levels detected were below the indicated LCIs and were approximately tenfold lower than the corresponding LCI for MT-limonene (50.88 vs. 5000 μg m -3 ) and eightfold (6.63 μg m -3 ) higher than the constitutive emission level for LOX-cis-3-hexenal. Over extended sampling (10 min) findings revealed a general emission decrease and significantly different CO 2 concentration between the assays. Despite similar decreasing rates of predicted net photosynthesis (Pn) and stomatal conductance (g s ) their correlation with decreasing CO 2 under uncontrolled condition indirectly suggested a negative CO 2 impact on plant emission activity. Conversely, increasing CO 2 under the controlled assay showed a positive correlation with induced emissions but not with constitutive ones. Because of significantly higher levels of relative humidity registered under the uncontrolled condition, this factor was considered to affect more than CO 2 the emission response and even its collection. This hypothesis was supported by literature findings and attributed to a common issue related with the sampling in static enclosure. Hence, we suggested a careful monitoring of the sampling conditions or further improvements to avoid bias and underestimation of actual emissions. Based on the main outcomes, we observed no evidence of a hazardous effect of registered CO 2 rates on the BVOC emissions of tomato plant. Furthermore, because of the low BVOC levels measured in the i-RTG, we assumed as safe the recirculation of this air along building's indoor environments., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xavier Gabarrell reports financial support was provided by 10.13039/501100004837Spain Ministry of Science and Innovation. Francesco Orsini reports financial support was provided by 10.13039/100010678H2020 Food Security Sustainable Agriculture and Forestry Marine Maritime and Inland Water Research and the Bioeconomy. Gaia Stringari reports was provided by 10.13039/501100002809Government of Catalonia Agency for Administration of University and Research Grants. Gara Villalba reports financial support was provided by 10.13039/501100000781European Research Council. Joan Villanueva reports financial support was provided by 10.13039/501100000781European Research Council., (© 2023 The Authors. Published by Elsevier Ltd.)

Introduction: This study aims to examine the potential effectiveness of intravenous neridronate (IVNer) on axial involvement in patients with spondyloarthritis (SpA) refractory to non-steroidal anti-inflammatory drugs (NSAIDs) but not eligible for biological disease-modifying antirheumatic drugs (bDMARDs)., Method: Patients with active SpA (BASDAI score ≥ 4) and active sacroiliitis (SI) on MRI (according to ASAS MRI definition), who were NSAID-insufficient responder/intolerant but not eligible for bDMARDs, were retrospectively recruited in a tertiary rheumatology centre between September 2015 and December 2021. IVNer (100 mg) was administered to the patients on days 1, 4, 7, and 10. Responses were evaluated 60 days after the last infusion as the median changes from the baseline of BASDAI and Visual Analogue Scale (VAS) pain and there are improvements on MRI signs., Results: A total of 38 patients (26 axial SpA, 3 enteropathic arthritis, and 9 axial psoriatic arthritis) were included [66% women, mean age ± SD: 38.0 ± 14.1 years, mean disease duration: 30.5 ± 49.5 months (range 1.0-298), 47% HLAB27+]. The reason for bDMARD ineligibility was concurrent solid tumors ( n  = 6) or hematological ( n  = 1) malignancy, comorbidities ( n  = 11), or patient preference ( n  = 20). Both median BASDAI [5.83 (4.2-8.33) versus 3.66 (1.1-6.85), p  < 0.001] and VAS pain [7 (5.75-8.0) versus 3 (1.0-7.0), p  < 0.0001] significantly decreased after IVNer. Of 28 available MRI at follow-up, we observed a complete (36%) or partial (39%) resolution of sacroiliitis or a persistent activity (25%)., Discussion: IVNer was effective in improving axial involvement in patients with SpA refractory to NSAIDs but not eligible for bDMARDs. IVNer can be considered as a potential alternative therapeutic option in selected settings., Competing Interests: MV served as a consultant for Abiogen. RC received speaker’s fee and consultation fee from Abbvie, BMS, Lilly, Galapgos, Fresenius-Kabi, MSD, UCB, and Pfizer. The remaining 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 Crotti, Di Taranto, Orsini, Ferrito, Varenna, Favalli and Caporali.)

The Spring transition to Daylight Saving Time (DST) has been associated with several health and road safety issues. Previous literature has focused primarily on the analysis of historical crash and hospitalization data, without investigating specific crash contributing factors, such as driving fatigue. The present study aims to uncover the effects of DST-related circadian desynchrony and sleep deprivation on driving fatigue, by means of a driving simulator experiment. Eighteen participants (all males, age range 21-30 years, mean = 24.2, SD = 2.9) completed two 50-minute trials (at one week distance, same time and same day of the week) on a monotonous highway environment, the second one taking place in the week after the Spring transition to DST. Driving fatigue was evaluated by analysing several different variables (including driving-based, physiological and subjective indices) and by comparison with a historical cohort of pertinent, matched controls who had also undergone two trials, but in the absence of any time change in between. Results showed a considerable rise in fatigue levels throughout the driving task in both trials, but with significantly poorer performance in the post-DST trial, documented by a worsening in vehicle lateral control and an increase in eyelid closure. However, participants seemed unable to perceive this decrease in their alertness, which most likely prevented them from implementing fatigue-coping strategies. These findings indicate that DST has a detrimental effect on driving fatigue in young male drivers in the week after the Spring transition, and provide valuable insights into the complex relationship between DST and road safety., 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., (© 2023 The Author(s).)

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.

Objective: Nurse home visiting (NHV) is designed to redress child and maternal health inequities. Of the previous trials to investigate NHV benefits beyond preschool, none were designed for populations with universal healthcare. To address this evidence gap, we investigated whether the Australian 'right@home' NHV programme improved child and maternal outcomes when children turned 6 and started school., Methods: A screening survey identified pregnant women experiencing adversity from antenatal clinics across two states (Victoria, Tasmania). 722 were randomised: 363 to the right@home programme (25 visits promoting parenting and home learning environment) and 359 to usual care. Child measures at 6 years (first school year): Strengths and Difficulties Questionnaire (SDQ), Social Skills Improvement System (SSIS), Childhood Executive Functioning Inventory (CHEXI) (maternal/teacher-reported); general health and paediatric quality of life (maternal-reported) and reading/school adaptation items (teacher-reported). Maternal measures: Personal Well-being Index (PWI), Depression Anxiety Stress Scales, warm/hostile parenting, Child-Parent Relationship Scale (CPRS), emotional abuse and health/efficacy items. Following best-practice methods for managing missing data, outcomes were compared between groups (intention-to-treat) using regression models adjusted for stratification factors, baseline variables and clustering (nurse/site level)., Results: Mothers reported on 338 (47%) children, and teachers on 327 (45%). Patterns of group differences favoured the programme arm, with small benefits (effect sizes ranging 0.15-0.26) evident for SDQ, SSIS, CHEXI, PWI, warm parenting and CPRS., Conclusions: Four years after completing the right@home programme, benefits were evident across home and school contexts. Embedding NHV in universal healthcare systems from pregnancy can offer long-term benefits for families experiencing adversity., Trial Registration Number: ISRCTN89962120., Competing Interests: Competing interests: The 'right@home' sustained nurse home visiting trial is a research collaboration between the Australian Research Alliance for Children and Youth (ARACY); the Translational Research and Social Innovation (TReSI) Group at Western Sydney University and the Centre for Community Child Health (CCCH), which is a department of The Royal Children’s Hospital and a research group of Murdoch Children’s Research Institute. Ownership of the right@home implementation and support license, which is purchased by Australian state governments for roll out for fidelity support, is shared between institutes., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed., Methods: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25-28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a 'study team' uninvolved in clinical care including decision-making. Procedure duration and the study team's words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: -0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated., Results: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65-0.70). The Bang index was 0.28 (95% CI 0.23-0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12-0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm., Conclusion: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified., Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age., Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022., Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment., Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years., Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90])., Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life., Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

The prevalence of overweight and obesity is continuously increasing, both in the adult and pediatric populations, posing a substantial challenge to public health. Understanding the epidemiological burden of metabolic syndrome (MetS) among children, particularly regarding its complications and long-term effects in adulthood, is crucial for identifying effective preventive measures and enhancing the clinical care of obese children. Therefore, by searching two databases, a systematic review was conducted in order to evaluate studies that specifically addressed the epidemiological MetS impact among overweight/obese European children and adolescents. Overall, 15 studies were considered. The epidemiological data concerning the MetS impact were contingent on the diagnostic criteria used and varied across countries, resulting in a prevalence range of 1.44% to 55.8%. Spanish studies were the most numerous (34%), revealing a country prevalence rate ranging from 2.5% to 19.6%. Males (prevalence range: 1.4-55.8%) and subjects with overweight/obesity (prevalence range: 12.9-55.8%) were mainly affected. Obesity emerged as the main risk factor in the MetS development and the consequent onset of cardiovascular complications and diabetes. Knowing the MetS burden and its risk factors could improve their prevention, detection, and treatment, and guide the development of targeted public health interventions to appropriately address the health needs of younger patients.

Objective: To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE)., Methods: We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA., Results: Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions)., Conclusions: Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA., Competing Interests: Author EF has been a consultant for and/or received honoraria as a speaker for the companies AbbVie, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, and UCB Pharma. Author MB received honoraria as a speaker for the company Galapagos. Author RC has been a consultant for and/or received honoraria as a speaker for the companies AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma. The remaining 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 Favalli, Cincinelli, Germinario, Di Taranto, Orsini, Maioli, Biggioggero, Ferrito and Caporali.)

In this study, we investigated how the COVID-19 pandemic involved osteoporosis care in patients treated with denosumab. Almost a third of patients missed the prescription renewal, mandatory to obtain the subsidized drug. Among patients who suspended denosumab, more than half reported fragility fractures., Purpose: This study aimed to evaluate persistence on denosumab (Dmab) treatment during the COVID-19 pandemic and the clinical effects of possible discontinuation., Methods: We retrospectively assessed patients affected by osteoporosis and treated with Dmab, scheduled to have the yearly renewal of prescription between March 9, 2020, and May 9, 2021, 2 months after the second pandemic wave. In June 2022, a telephone survey started, by calling all patients who missed the yearly renewal of Dmab. Predictors of missed renewal and fragility fracture occurrence were assessed by logistic analyses., Results: Patients scheduled to have a renewal of Dmab prescription during the observational period were 538 (age 75.5 ± 9.3 years, female 511). A total of 152 (28.2%) patients did not have the renewal. Patients not renewing Dmab prescription were significantly older (p = 0.01) and more frequently affected by pulmonary (p = 0.04) and cardiovascular comorbidity (p = 0.01). Telephone survey on non-persistent patients showed that 44 had died, 28 patients were missing, 23 shifted to bisphosphonate treatment, and 22 patients suspended Dmab. Following discontinuation, 12/22 patients (54.5%) reported fragility fractures; 5/22 had multiple fractures, for a total number of 18 fractures, mainly vertebral. Logistic analyses showed that the odds of Dmab withdrawal increased in older patients with pulmonary comorbidity and treated for a shorter time. Dmab discontinuation was the only variable that increased the risk of fracture., Conclusion: This study provided real-world data about an impaired persistence of Dmab treatment resulting in an increased number of fragility fractures in a geographic area heavily affected by the outbreak of COVID-19., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy., Methods: A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5-15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range. The treatment group received a rigid wrist-hand orthosis, to wear ≥6 h per night for 3 years. Analysis included repeated measures mixed-effects linear regression models, using intention-to-treat principles., Results: The trial stopped early due to insufficient recruitment: 74 children, across all Manual Ability Classification System levels, were randomised ( n  = 38 orthosis group; n  = 36 control). Mean age was 10.2 (SD 3.1) years (orthosis group) and 9.1 (SD 2.8) years (control). Data showed some evidence that rigid wrist-hand orthosis impacted passive wrist extension with fingers extended in the first year [mean difference between-groups at 6 months: 13.15° (95%CI: 0.81-25.48°, p  = 0.04); 12 months: 20.94° (95%CI: 8.20-33.69°, p  = 0.001)]. Beyond 18 months, participant numbers were insufficient for conclusive findings., Conclusion: The study provided detailed data about short- and long-term effects of the wrist-hand orthosis and highlighted challenges in conducting large randomised controlled trials with this population. Trial Registration: Australia and New Zealand Clinical Trials Registry: U1111-1164-0572 IMPLICATIONS FOR REHABILITATIONThere may be incremental benefit, for children with cerebral palsy, at 6 and 12 months on passive wrist range from wearing a rigid wrist-hand orthosis designed according to this protocol.The rigid-wrist-hand orthosis evaluated in this study, which allowed for some tailoring for individual children's presentations, differed in design from past recommendations for "resting hand" positioning.Longitudinal follow up of children with cerebral palsy prescribed a rigid wrist-hand orthosis is essential to monitor any benefit.Minor adverse events were commonly experienced when wearing the orthosis and should be discussed prior to prescription of a rigid wrist-hand orthosis.

In recent years, the adoption of teleworking has witnessed a significant surge, partly driven by the COVID-19 pandemic. The existing literature suggests that its implementation has elicited mixed reactions from workers; while some workers have expressed satisfaction with its introduction, others prefer to work in a traditional, on-site setting. Concurrently, there has been a growing interest in Mobility-as-a-Service (MaaS) and an increase in the number of companies offering such services. However, there is limited research exploring the relationship between teleworking and the utilization of MaaS. This paper aims to fill this gap, by analyzing (1) which factors influence users to adopt teleworking in a post-pandemic scenario and (2) the relationship between willingness to telework and the propensity to join a MaaS system. An ordered logit model and a mixed logit model were developed to achieve the two goals, respectively. These models were calibrated and validated using data collected from questionnaires administered to Padua Municipality employees between October 2020 and January 2021. As expected, the employees most inclined toward teleworking are those who seek more flexibility and are unable to commute by private means. In addition, results show that employees who expressed the preference to telework more in the future are less likely to adopt MaaS, suggesting that the increased popularity of teleworking due to the pandemic may have a negative effect on the uptake of MaaS. These findings were utilized to formulate several policy recommendations., 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., (© 2023 World Conference on Transport Research Society. Published by Elsevier Ltd. All rights reserved.)

Urban green installations are extensively promoted to increase sustainable and accessible food production and simultaneously improve the environmental performance and liveability of city buildings. In addition to the multiple benefits of plant retrofitting, these installations may lead to a consistent increase in biogenic volatile organic compounds (BVOCs) in the urban environment, especially indoors. Accordingly, health concerns could limit the implementation of building-integrated agriculture. In a building-integrated rooftop greenhouse (i-RTG), throughout the whole hydroponic cycle, green bean emissions were dynamically collected in a static enclosure. Four representative BVOCs, α-pinene (monoterpene), β-caryophyllene (sesquiterpene), linalool (oxygenated monoterpene) and cis-3-hexenol (LOX derivate), were investigated in the samples collected from two equivalent sections of a static enclosure, one empty and one occupied by the i-RTG plants, to estimate the volatile emission factor (EF). Throughout the season, extremely variable BVOC levels between 0.04 and 5.36 ppb were found with occasional but not significant (P > 0.05) variations between the two sections. The highest emission rates were observed during plant vegetative development, with EFs equivalent to 78.97, 75.85 and 51.34 ng g -1  h -1 for cis-3-hexenol, α-pinene, and linalool, respectively; at plant maturity, all volatiles were either close to the LLOQ (lowest limit of quantitation) or not detected. Consistent with previous studies significant relationships (r ≥ 0.92; P < 0.05) were individuated within volatiles and temperature and relative humidity of the sections. However, correlations were all negative and were mainly attributed to the relevant effect of the enclosure on the final sampling conditions. Overall, levels found were at least 15 folds lower than the given Risk and LCI values of the EU-LCI protocol for indoor environments, suggesting low BVOC exposure in the i-RTG. Statistical outcomes demonstrated the applicability of the static enclosure technique for fast BVOC emissions survey inside green retrofitted spaces. However, providing high sampling performance over entire BVOCs collection is recommended to reduce sampling error and incorrect estimation of the emissions., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19)., Methods: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline., Results: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified., Conclusions: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.)., (Copyright © 2023 Massachusetts Medical Society.)

Coenzyme Q 10 (CoQ 10 ) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ 10 uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ 10 content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ 10 following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ 10 for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ 10 crystalline form. After supplementation, plasma was collected for CoQ 10 determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ 10 content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ 10 -enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ 10 to skin and muscle tissues.

Targeted axillary dissection (TAD) is an axillary staging technique after NACT that involves the removal of biopsy-proven metastatic lymph nodes in addition to sentinel lymph node biopsy (SLNB). This technique avoids the morbidity of traditional axillary lymph node dissection and has shown a lower false-negative rate than SLNB alone. Therefore, marking positive axillary lymph nodes before NACT is critical in order to locate and remove them in the subsequent surgery. Current localization methods include clip placement with intraoperative ultrasound, carbon-suspension liquids, localization wires, radioactive tracer-based localizers, magnetic seeds, radar reflectors, and radiofrequency identification devices. The aim of this paper is to illustrate the management of axillary lymph nodes based on current guidelines and explain the features of axillary lymph node markers, with relative advantages and disadvantages.

In this perspective article, we present a short selection of some of the most significant case studies on magnetic nanoparticles for potential applications in nanomedicine, mainly magnetic resonance. For almost 10 years, our research activity focused on the comprehension of the physical mechanisms on the basis of the nuclear relaxation of magnetic nanoparticles in the presence of magnetic fields; taking advantage of the insights gathered over this time span, we report on the dependence of the relaxation behaviour on the chemico-physical properties of magnetic nanoparticles and discuss them in full detail. In particular, a critical review is carried out on the correlations between their efficiency as contrast agents in magnetic resonance imaging and the magnetic core of magnetic nanoparticles (mainly iron oxides), their size and shape, and the coating and solvent used for making them biocompatible and well dispersible in physiological media. Finally, the heuristic model proposed by Roch and coworkers is presented, as it was extensively adopted to describe most of the experimental data sets. The large amount of data analyzed allowed us to highlight both the advantages and limitations of the model.

The City Region Food Systems approach has been proposed to achieve food system resilience and nutrition security while promoting the urgent ecological transition within urban and peri-urban areas, especially after the COVID-19 pandemic. However, the great diversity of the initiatives composing City Region Food Systems in Europe poses barriers to the assessment of their integrated sustainability. Hence, the present work is developed within the EU-H2020 project Food System in European Cities (FoodE), to build a consistent sustainability scoring system that allows comparative evaluation of City Region Food System Initiatives. Adopting a Life Cycle Thinking approach, it advances on existing knowledge and past projects, taking advantage of a participatory process, with stakeholders from multidisciplinary expertise. As a result, the research designs, and tests on 100 case studies a simplified and ready-to-use scoring mechanism based on a quali-quantitative appraisal survey tool, delivering a final sustainability score on a 1-5 points scale, to get insights on the social, economic, and environmental impacts. As in line with the needs of the UN Sustainable Development Goals, the outcome represents a step forward for the sustainable development and social innovation of food communities in cities and regions, providing a practical and empirical lens for improved planning and governance., Competing Interests: None., (© 2022 Published by Elsevier Ltd on behalf of Institution of Chemical Engineers.)

Despite sleepiness being considered one of the main factors contributing to road crashes, and even though extensive efforts have been made in the identification of techniques able to detect it, the assessment of fitness-to-drive regarding driving fatigue and sleepiness is still an open issue. In the literature on driver sleepiness, both vehicle-based measures and behavioral measures are used. Concerning the former, the one considered more reliable is the Standard Deviation of Lateral Position (SDLP) while the PERcent of eye CLOSure over a defined period of time (PERCLOS) seems to be the most informative behavioral measure. In the present study, using a within-subject design, we assessed the effect of a single night of partial sleep deprivation (PSD, less than 5 h sleeping time) compared to a control condition (full night of sleep, 8 h sleeping time) on SDLP and PERCLOS, in young adults driving in a dynamic car simulator. Results show that time-on-task and PSD affect both subjective and objective sleepiness measures. Moreover, our data confirm that both objective and subjective sleepiness increase through a monotonous driving scenario. Considering that SDLP and PERCLOS were often used separately in studies on driver sleepiness and fatigue detection, the present results have potential implications for fitness-to-drive assessment in that they provide useful information allowing to combine the advantages of the two measures for drowsiness detection while driving.

We investigated the effect of different organic coatings on the 1 H-NMR relaxation properties of ultra-small iron-oxide-based magnetic nanoparticles. The first set of nanoparticles, with a magnetic core diameter ds1 = 4.4 ± 0.7 nm, was coated with polyacrylic acid (PAA) and dimercaptosuccinic acid (DMSA), while the second set, ds2 = 8.9 ± 0.9 nm, was coated with aminopropylphosphonic acid (APPA) and DMSA. At fixed core diameters but different coatings, magnetization measurements revealed a similar behavior as a function of temperature and field. On the other hand, the 1 H-NMR longitudinal r1 nuclear relaxivity in the frequency range ν = 10 kHz ÷ 300 MHz displayed, for the smallest particles (diameter ds1), an intensity and a frequency behavior dependent on the kind of coating, thus indicating different electronic spin dynamics. Conversely, no differences were found in the r1 relaxivity of the biggest particles (ds2) when the coating was changed. It is concluded that, when the surface to volume ratio, i.e., the surface to bulk spins ratio, increases (smallest nanoparticles), the spin dynamics change significantly, possibly due to the contribution of surface spin dynamics/topology.

We present an investigation of the effects on BxPC3 pancreatic cancer cells of proton therapy combined with hyperthermia, assisted by magnetic fluid hyperthermia performed with the use of magnetic nanoparticles. The cells' response to the combined treatment has been evaluated by means of the clonogenic survival assay and the estimation of DNA Double Strand Breaks (DSBs). The Reactive Oxygen Species (ROS) production, the tumor cell invasion and the cell cycle variations have also been studied. The experimental results have shown that the combination of proton therapy, MNPs administration and hyperthermia gives a clonogenic survival that is much smaller than the single irradiation treatment at all doses, thus suggesting a new effective combined therapy for the pancreatic tumor. Importantly, the effect of the therapies used here is synergistic. Moreover, after proton irradiation, the hyperthermia treatment was able to increase the number of DSBs, even though just at 6 h after the treatment. Noticeably, the magnetic nanoparticles' presence induces radiosensitization effects, and hyperthermia increases the production of ROS, which contributes to cytotoxic cellular effects and to a wide variety of lesions including DNA damage. The present study indicates a new way for clinical translation of combined therapies, also in the vision of an increasing number of hospitals that will use the proton therapy technique in the near future for different kinds of radio-resistant cancers.

African agriculture is bound to face challenges for its future food systems development and economic transformation. Indoor vertical farms with artificial lighting represent an opportunity that has been gaining relevance worldwide, thanks to their potential to enable high productivity rates, food quality and safety, year-round production, and more sustainable use of water and mineral nutrients. The present study assesses the potential for vertical farming technology integration within the African continent, targeting the countries where a more sustainable approach could be achieved. A deep analysis of each territory's major opportunities and challenges was built through an updated database of 147 development indicators from 54 African states. Countries such as South Africa, Seychelles, Egypt, Mauritius, Morocco, Tunisia, Algeria, Cape Verde, and Nigeria showed the best prospective for indoor vertical farming implementation. Moreover, Seychelles, South Africa, and Egypt resulted to be the countries where vertical indoor farming could be more sustainable., (© 2023. The Author(s).)

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science., (open access.)

Objectives: Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program ("right@home") in promoting children's language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years., Setting and Participants: Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia., Intervention: Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1-43] received) of 60-90 minutes, commencing antenatally and continuing until children's second birthdays., Primary and Secondary Outcomes Measured: At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children's language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting., Results: Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01-0·27., Conclusion: An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing adversity. NHV can offer an important component of a proportionate universal system that delivers support and intervention relative to need., Trial Registration: 2013-2016, registration ISRCTN89962120., Competing Interests: The “right@home” sustained nurse home visiting trial is a research collaboration between the Australian Research Alliance for Children and Youth (ARACY); the Translational Research and Social Innovation (TReSI) Group at Western Sydney University; and the Centre for Community Child Health (CCCH), which is a department of The Royal Children’s Hospital and a research group of Murdoch Children’s Research Institute. Ownership of the right@home implementation and support licence, which is purchased by Australian state governments for roll out, is shared between institutes., (Copyright: © 2022 Goldfeld 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.)

Light composition modulates plant growth and defenses, thus influencing plant-pathogen interactions. We investigated the effects of different light-emitting diode (LED) red (R) (665 nm) and blue (B) (470 nm) light combinations on Actinidia chinensis performance by evaluating biometric parameters, chlorophyll a fluorescence, gas exchange and photosynthesis-related gene expression. Moreover, the influence of light on the infection by Pseudomonas syringae pv. actinidiae (Psa), the etiological agent of bacterial canker of kiwifruit, was investigated. Our study shows that 50%R-50%B (50R) and 25%R-75%B (25R) lead to the highest PSII efficiency and photosynthetic rate, but are the least effective in controlling the endophytic colonization of the host by Psa. Monochromatic red light severely reduced ΦPSII, ETR, Pn, TSS and photosynthesis-related genes expression, and both monochromatic lights lead to a reduction of DW and pigments content. Monochromatic blue light was the only treatment significantly reducing disease symptoms but did not reduce bacterial endophytic population. Our results suggest that monochromatic blue light reduces infection primarily by modulating Psa virulence more than host plant defenses.

A clear relationship between the tau assemblies and toxicity has still to be established. To correlate the tau conformation with its proteotoxic effect in vivo, we developed an innovative cell-worm-based approach. HEK293 cells expressing tau P301L under a tetracycline-inducible system (HEK T-Rex) were employed to produce different tau assemblies whose proteotoxic potential was evaluated using C. elegans . Lysates from cells induced for five days significantly reduced the worm's locomotor activity. This toxic effect was not related to the total amount of tau produced by cells or to its phosphorylation state but was related to the formation of multimeric tau assemblies, particularly tetrameric ones. We investigated the applicability of this approach for testing compounds acting against oligomeric tau toxicity, using doxycycline (Doxy) as a prototype drug. Doxy affected tau solubility and promoted the disassembly of already formed toxic aggregates in lysates of cells induced for five days. These effects translated into a dose-dependent protective action in C. elegans . These findings confirm the validity of the combined HEK T-Rex cells and the C. elegans -based approach as a platform for pharmacological screening.

Background: A high proportion of patients with neurofibromatosis type 1 (NF1) present with functional hearing deficiency as a result of neural abnormality in the late auditory brainstem., Methods: In this randomized, two-period crossover study, we investigated the hypothesis that remote-microphone listening devices can ameliorate hearing and communication deficits in affected school-aged children (7-17 years). Speech perception ability in background noise was evaluated in device-active and inactive conditions using the CNC-word test. Participants were then randomized to one of two treatment sequences: (1) inactive device for two weeks (placebo), followed by active device use for two weeks, or (2) active device for 2 weeks, followed by inactive device for 2 weeks. Listening and communication ratings (LIFE-R Questionnaire) were obtained at baseline and at the end of each treatment phase., Results: Each participant demonstrated functional hearing benefits with remote-microphone use. All showed a speech perception in noise increase when the device was activated with a mean phoneme-score difference of 16.4% (p < 0.001) and reported improved listening/communication abilities in the school classroom (mean difference: 23.4%; p = 0.017)., Discussion: Conventional hearing aids are typically ineffective as a treatment for auditory neural dysfunction, making sounds louder, but not clearer for affected individuals. In this study, we demonstrate that remote-microphone technologies are acceptable/tolerable in pediatric patients with NF1 and can ameliorate their hearing deficits., Conclusion: Remote-microphone listening systems offer a viable treatment option for children with auditory deficits associated with NF1., (© 2022. The Author(s).)

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.

Background: Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals., Methods: A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian (n = 20) and New Zealand (n = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qualitative component will consist of semi-structured interviews with three to five key emergency department and paediatric inpatient medical and nursing staff per site (total n = 78-130). Factors that may have contributed to sustaining outcomes and/or interventions will be explored and mapped to an established sustainability framework., Discussion: This study will improve our understanding of the sustainability of evidence-based bronchiolitis management in infants. Results will also advance implementation science research by informing future de-implementation strategies to reduce low-value practices and sustain practice change in paediatric acute care., Trial Registration: Australian and New Zealand Clinical Trials Registry No: ACTRN12621001287820., (© 2022. The Author(s).)