Search

BACKGROUND: Inappropriate use of antibiotics is one of the important factors attributing to emergence of drug-resistant pathogens. Infection with multidrug-resistant pathogens adversely affects quality of medical care. CONTEXT: Queen Elizabeth Hospital, an 1800-bed acute service hospital in Hong Kong. Antibiotics are commonly prescribed for treating acute infections. KEY MEASURES FOR IMPROVEMENT: Reduce inappropriate prescription of broad-spectrum antibiotics and overall antibiotic prescription through implementation of a multidisciplinary antibiotics stewardship programme (ASP). STRATEGIES FOR CHANGE: A multidisciplinary programme involving policy and guideline formulation, education and feedback, monthly antibiotic consumption and cost monitoring, antimicrobial susceptibility pattern reporting and concurrent feedbacks for commonly prescribed broad-spectrum antibiotics was implemented in 2004. Predefined logistics to prescribe 'restricted' antibiotics were formulated and implemented with collaborative efforts from clinical and non-clinical departments. The programme was supported by management at department and hospital levels. EFFECTS OF CHANGE: Broad-spectrum antibiotics were prescribed inappropriately in 28.9% (n = 192) clinical scenarios. The ASP reduced the restricted and total antibiotic consumption as well as the antibiotics-related costs. Predefined clinical outcomes were not adversely affected. Economic analysis suggested that the extra human cost in running ASP could be offset by savings from antibiotic expenditure. LESSONS LEARNED: It is cost-effective to implement a multidisciplinary ASP in acute service hospitals as the programme reduces antibiotic consumption and results in overall cost savings. The quality of medical care is not jeopardized as the important clinical outcomes are not adversely affected. The generalisability and sustainability of ASPs in other clinical contexts warrant further studies to ensure the continuous success of this programme. [ABSTRACT FROM AUTHOR]

Background: The increasing utilizationof human UC blood (UCB) in transplantation has drawn attention to the need for rationalization of selection, collection, processing, testing, banking and release of UCB. However, the issue of maternal blood contamination has not been well addressed. There are concerns that maternal T cells might elicit GvHD post-UCB transplant. Methods: Maternal T cells in 58 male UCB allografts were enumerated using fluorescent in situ hybridization and flow cytometry. Obstetric factors, preceding labor, multi-parity and gestational age, were also analyzed. Results: Levels of maternal cells of 0.75-5.25% were found in 15.5% (9/58) UCB. There was no association of maternal-cell contamination with preceding labor [25% (2/8) with previous delivery versus 35.4% (17/48) first born, P = 0.702], nor any correlation with multi-parity [37.5% (3/8) para ≥ 3 versus 16.7% (8/48) para < 3, P = 0.181]. Gestation age of newborns also exhibited no association with maternal-cell contamination (39.47 weeks in newborn UCB with maternal cells, versus 39.58 weeks without: P = 0.674). The extrapolated maternal T cells/kg in nine UCB transplants were 1.05 × 10[sup 5] ± 1.12 × 10[sup 5] (3.40 × 10[sup 4] - 3.18 × 10[sup 5]). Discussion: In relation to the arbitrary threshold of 1 × 10[sup 5] T cells/kg in HLA-mismatched transplants utilizing T-cell depleted BM, 22.2% (2/9) of UCB transplants having maternal-cell contamination might be at risk of GvHD. Data support the need for testing for maternal blood in UCB, and evaluating the clinical relevance of GvHD in patients post-UCB transplant. The establishment of guidelines and standards for release of such UCB collections would be advisable in evidence-based UCB transplantation. [ABSTRACT FROM AUTHOR]

Refractory supraventricular tachyarrhythmias may he both difficult and costly to control medically and can interfere with the patient's lifestyle. Newer treatment modalities are available for their management, and these require comprehensive assessment. We therefore compared costs and selective indices of patient benefit in a group of 17 patients in whom an atrial antitachycardia (Intermedics Intertach 262-12) pacemaker was placed for refractory supraventricular tachyarrhythmias. Prior medical therapy was compared to subsequent automatic antitachycardia pacemaker treatment. The total medical costs (admissions, emergency room visits, office visits, and medication costs) and the number of hospitalizations and medications were compared prior to implantation (F/U 69.3 ± 61 months) and after implantation (F/U 15.3 ± 7.8 months). A detailed quality-of-life questionnaire was also obtained 36.6 ± 11 months after implantation. Results: There were significant per patient differences in total cost before and after implantation: monthly costs were $505 ± $833 before pacemaker implantation and $105 ± $117 monthly afterward (P < 0.005). Pacemaker implantation hospitalization costs were $19,063 ± $8,362. Monthly medication costs averaged $46 before versus $15 after implantation (P < 0.01). The number of medication types also differed with an average 5.5 medication types per patient before versus 1.2 after implantation (P < 0.001]. There were 8.6 yearly hospital admissions in the whole group before implantation, versus 4.7 admissions in the group per year thereafter. Patients demonstrated significant improvement in 80% of the quality-of-life parameters studied. Conclusion: Adjunctive atrial automatic tachycardia-reversion pacemaker therapy may be cost-competitive over time when compared to medical therapy alone in patients with refractory supraventricular tachyarrhythmias and appears to improve overall quality-of-life. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Pneumococcal conjugate vaccine (PCV) is an effective way to prevent invasive pneumococcal diseases in high risk populations. The efficacy of this vaccine in paediatric oncology patients remains unknown. DESIGN AND SETTING: The authors evaluated the antibody response to seven pneumococcal serotypes in paediatric oncology patients given two doses of heptavalent PCV (PCV-7). RESULTS: Forty-four patients (20 males; 24 females) with median age 9.5 years were studied. After two doses of PCV-7, 86-100% of patients had protective antibody titres against the seven vaccine serotypes. Increases in geometric mean antibody concentrations ranged from 3.8-fold for serotype 19F to 85.8-fold for serotype 14. There was no documented invasive pneumococcal disease in our cohort during the study period. CONCLUSION: PCV can elicit protective antipneumococcal antibody responses in paediatric oncology patients. [ABSTRACT FROM AUTHOR]

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous α-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment. [ABSTRACT FROM AUTHOR]

Inflammatory myofibroblastic tumour (IMFT) is a distinct entity under the group of inflammatory pseudotumours. Sometimes these pseudotumours can have an aggressive appearance on imaging, which makes it indistinguishable from other malignant neoplasms. We present a case of IMFT of the bladder in a child. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition., (©2024 American Association for Cancer Research.)

Measurement of proton spectra is an important diagnostic for a variety of high energy density physics experiments. Current diagnostics are either not designed to capture the spectrum of low-energy protons or are unsuitable for high debris experiments. To bridge the gap, a new CR-39 based compact magnetic spectrometer (MagSpec) has been developed to measure proton spectra in the 1-20 MeV energy range, with a particular focus on the low-energy (1-6 MeV) spectrum, for use in experiments at the OMEGA Laser Facility and the National Ignition Facility (NIF). In the MagSpec diagnostic, protons of different energies are dispersed as they pass through a magnetic field before impinging on a differentially filtered CR-39 surface, resulting in a spatial distribution of CR-39 tracks that corresponds to the energy spectrum. In this paper, we discuss details of the design and implementation of MagSpec on the NIF and OMEGA., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Introduction: This cross-sectional survey research investigated mental health symptoms and quality of life among Chinese parents and their children with eczema at a paediatric dermatology clinic in Hong Kong from November 2018 to October 2020., Methods: Health-related quality of life, eczema severity, and mental health among children with eczema, as well as their parents' mental health, were studied using the Children's Dermatology Life Quality Index (CDLQI), Infants' Dermatitis Quality of Life Index (IDQOL), Nottingham Eczema Severity Score (NESS), Patient-Oriented Eczema Measure (POEM), and the Chinese version of the 21-item Depression, Anxiety, and Stress Scales (DASS-21)., Results: In total, 432 children and 380 parents were recruited. Eczema severity (NESS and POEM) and health-related quality of life (CDLQI) were significantly positively associated with parental and child depression, anxiety, and stress levels according to the DASS-21, regardless of sex (children: r=0.28- 0.72, P<0.001 to 0.007; parents: r=0.20-0.52, P<0.001 to 0.034). Maternal depression was marginally positively associated with increased anxiety in boys with eczema (r=0.311; P=0.045). Younger parents had higher risk of developing more anxiety and stress compared with the older parents (adjusted odds ratio [aOR]=-0.342, P=0.014 and aOR=-0.395, P=0.019, respectively). Depression level of parents with primary to secondary education was 58% higher than their counterparts with post-secondary education or above (aOR=-1.579; P=0.007)., Conclusion: Depression, anxiety, and stress among children with eczema and their parents were associated with eczema severity and impaired quality of life in those children. These findings regarding impaired mental health in children with eczema and their parents highlight the need to include mental well-being and psychosocial outcomes in future studies and clinical practice., Competing Interests: As an editor of the journal, KL Hon was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

The Particle Time of Flight (PTOF) detector is a chemical vapor deposition diamond-based detector used to measure bang times in low-yield (≲ 1015 neutrons) experiments at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL). Historically, the impulse response for PTOF diamond detectors has been obtained from x-ray timing shots on the NIF and shots on the MegaRay pulsed electron accelerator at LLNL. The impulse response may alternatively be obtained using single particle interactions with the detector, at substantially less cost and higher frequency compared to NIF timing shots, which typically occur months apart. Here, the response of a PTOF detector setup is characterized by statistically averaging a large number of single particle waveforms. A high fidelity instrument response function can be constructed in this way. This is confirmed by comparison of the single particle counting-constructed response to the impulse response function measured for the same detector at LLNL's MegaRay facility., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Image plates (IPs) are a quickly recoverable and reusable radiation detector often used to measure proton and x-ray fluence in laser-driven experiments. Recently, IPs have been used in a proton radiography detector stack on the OMEGA laser, a diagnostic historically implemented with CR-39, or radiochromic film. The IPs used in this and other diagnostics detect charged particles, neutrons, and x-rays indiscriminately. IPs detect radiation using a photo-stimulated luminescence (PSL) material, often phosphor, in which electrons are excited to metastable states by ionizing radiation. Protons at MeV energies deposit energy deeper into the IP compared with x rays below ∼20 keV due to the Bragg peak present for protons. This property is exploited to discriminate between radiation types. Doses of mono-energetic protons between 1.7 and 14 MeV are applied to IPs using the MIT linear electrostatic ion accelerator. This paper presents the results from consecutive scans of IPs irradiated with different proton energies. The PSL ratios between subsequent scans are shown to depend on proton energy, with higher energy protons having lower PSL ratios for each scan. This finding is separate from the known energy dependence in the absolute sensitivity of IPs. The results can be compared to complimentary work on x rays, showing a difference between protons and x rays, forging a path to discriminate between proton and x-ray fluence in mixed radiation environments., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Background: IKZF1 deletion (IKZF1 del ) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1 del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined., Methods: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1 del patients were further divided based on chemotherapy intensity for outcome assessments., Results: The BCP-ALL pediatric patients with IKZF1 del in south China showed poorer early response. Notably, the DFS and OS for IKZF1 del patients were markedly lower than IKZF1 wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1 del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1 del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026)., Conclusions: Pediatric BCP-ALL patients with IKZF1 del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1 del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1 del subset, particularly in IKZF del patients with BCR::ABL positive., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Objectives: Childhood cancer survivors may experience complex health issues during transition and long-term follow-up (LTFU); therefore, high-quality healthcare is warranted. Care coordination is one of the essential concepts in advanced healthcare. Care coordination models vary among childhood cancer survivors in transition and LTFU. This study aimed to identify care coordination models for childhood cancer survivors in transition and LTFU and synthesise essential components of the models., Design: This scoping review was guided by the methodological framework from Arksey and O'Malley and was reported with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic literature search was conducted on six databases using possible combinations of terms relevant to childhood cancer survivors, transition/LTFU and care coordination model. Data were analysed by descriptive and content analysis., Data Sources: The literature search was first conducted in May 2023 and updated in May 2024. Six databases including Medline, PubMed, Embase, Web of Science, CINAHL and Cochrane Library were searched; meanwhile, a hand search was also conducted., Eligibility Criteria for Selecting Studies: Studies relevant to describing any models, interventions or strategies about care coordination of transition or LTFU healthcare services among childhood cancer survivors were included., Data Extraction and Synthesis: Two reviewers independently screened and included studies. Basic information as well as care coordination model-related data in the included studies were extracted. Descriptive summary and content analysis were used for data analysis., Results: In the 20 545 citations generated by the search strategy, seven studies were identified. The critical determinants of the models in the included studies were the collaboration of the multidisciplinary team, integration of the navigator role and the provision of patient-centred, family-involved, needs-oriented clinical services. The main functions of the models included risk screening and management, primary care-based services, psychosocial support, health education and counselling, and financial assistance. Models of care coordination were evaluated at patient and clinical levels. Based on this review, core concepts of successful care coordination models for childhood cancer survivors in transition or LTFU were synthesised and proposed as the '3 I' framework: individualisation, interaction and integration., Conclusion: This scoping review summarised core elements of care coordination models for childhood cancer survivors' transition and LTFU. A proposed conceptual framework to support and guide the development of care coordination strategies for childhood cancer survivors' transition and LTFU care was developed. Future research is needed to test the proposed model and develop appropriate care coordination strategies for providing high-quality healthcare for childhood cancer survivors' transition and LTFU., Competing Interests: Competing interests: None declared., (© 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.)

Introduction: Communicating complex information about haemodialysis (HD) and ensuring it is well understood remains a challenge for clinicians. Informed consent is a high-impact checkpoint in augmenting patients' decision awareness and engagement prior to HD. The aims of this study are to (1) develop a digital information interface to better equip patients in the decision-making process to undergo HD; (2) evaluate the effectiveness of the co-designed digital information interface to improve patient outcomes; and (3) evaluate an implementation strategy., Methods and Analysis: First, a co-design process involving consumers and clinicians to develop audio-visual content for an innovative digital platform. Next a two-armed, open-label, multicentre, randomised controlled trial will compare the digital interface to the current informed consent practice among adult HD patients (n=244). Participants will be randomly assigned to either the intervention or control group. Intervention group: Participants will be coached to an online platform that delivers a simple-to-understand animation and knowledge test questions prior to signing an electronic consent form., Control Group: Participants will be consented conventionally by a clinician and sign a paper consent form. Primary outcome is decision regret, with secondary outcomes including patient-reported experience, comprehension, anxiety, satisfaction, adherence to renal care, dialysis withdrawal, consent time and qualitative feedback. Implementation of eConsent for HD will be evaluated concurrently using the Consolidation Framework for Implementation Research (CFIR) methodology., Analysis: For the randomised controlled trial, data will be analysed using intention-to-treat statistical methods. Descriptive statistics and CFIR-based analyses will inform implementation evaluation., Ethics and Dissemination: Human Research Ethics approval has been secured (Metro North Health Human Research Ethics Committee B, HREC/2022/MNHB/86890), and Dissemination will occur through partnerships with stakeholder and consumer groups, scientific meetings, publications and social media releases., Trial Registration Number: Australian and New Zealand Clinical Trials Registry (ACTRN12622001354774)., Competing Interests: Competing interests: PFG: Consentic shareholder; RBS: CEO of Consentic., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The environmental surveillance of air grilles in clinical areas has not been systematically analysed., Methods: Samples were collected from frequently touched items (N = 529), air supply (N = 295) and exhaust (N = 184) grilles in six medical and 11 surgical wards for the cultures of multi-drug-resistant organisms (MDROs): meticillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome sequencing (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs., Results: From 3 rd October to 21 st November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%, 24/99), CRAB (59.6%, 59/99) and CPE (2.0%, 2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%, 49/184) was significantly higher than in air supply grilles (5.8%, 17/295; P<0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%, 14/19) was significantly higher than in surgical wards (12.5%, 4/32; P<0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%, 13/48 vs 28.8%, 30/104; P=0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r = 0.878; 95% confidence interval (CI): 0.136-0.986; P=0.004), as well as with the contamination rate in air supply grilles (r = 0.960; 95% CI: 0.375-0.999; P<0.001) and air exhaust grilles (r = 0.850; 95% CI: 0.401-0.980; P=0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles., Conclusions: Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGF-β1-Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin ( DCN ), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-β and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity., Objective: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung., Material and Methods: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs- decorin , and decorin . Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted., Results: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-β levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis., Conclusion: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury., Competing Interests: There was no conflict of interest to declare.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1 H nuclear magnetic resonance ( 1 H NMR), 13 C nuclear magnetic resonance ( 13 C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A 24 demonstrated a strong efficacy with an EC 50 value of 7.8 μg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 μg/mL) and bismerthiazol (43.3 μg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A 24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A 24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Shock-driven implosions with 100% deuterium (D&#95;{2}) gas fill compared to implosions with 50:50 nitrogen-deuterium (N&#95;{2}D&#95;{2}) gas fill have been performed at the OMEGA laser facility to test the impact of the added mid-Z fill gas on implosion performance. Ion temperature (T&#95;{ion}) as inferred from the width of measured DD-neutron spectra is seen to be 34%±6% higher for the N&#95;{2}D&#95;{2} implosions than for the D&#95;{2}-only case, while the DD-neutron yield from the D&#95;{2}-only implosion is 7.2±0.5 times higher than from the N&#95;{2}D&#95;{2} gas fill. The T&#95;{ion} enhancement for N&#95;{2}D&#95;{2} is observed in spite of the higher Z, which might be expected to lead to higher radiative loss, and higher shock strength for the D&#95;{2}-only versus N&#95;{2}D&#95;{2} implosions due to lower mass, and is understood in terms of increased shock heating of N compared to D, heat transfer from N to D prior to burn, and limited amount of ion-electron-equilibration-mediated additional radiative loss due to the added higher-Z material. This picture is supported by interspecies equilibration timescales for these implosions, constrained by experimental observables. The one-dimensional (1D) kinetic Vlasov-Fokker-Planck code ifp and the radiation hydrodynamic simulation codes hyades (1D) and xrage [1D, two-dimensional (2D)] are brought to bear to understand the observed yield ratio. Comparing measurements and simulations, the yield loss in the N&#95;{2}D&#95;{2} implosions relative to the pure D&#95;{2}-fill implosion is determined to result from the reduced amount of D&#95;{2} in the fill (fourfold effect on yield) combined with a lower fraction of the D&#95;{2} fuel being hot enough to burn in the N&#95;{2}D&#95;{2} case. The experimental yield and T&#95;{ion} ratio observations are relatively well matched by the kinetic simulations, which suggest interspecies diffusion is responsible for the lower fraction of hot D&#95;{2} in the N&#95;{2}D&#95;{2} relative to the D&#95;{2}-only case. The simulated absolute yields are higher than measured; a comparison of 1D versus 2D xrage simulations suggest that this can be explained by dimensional effects. The hydrodynamic simulations suggest that radiative losses primarily impact the implosion edges, with ion-electron equilibration times being too long in the implosion cores. The observations of increased T&#95;{ion} and limited additional yield loss (on top of the fourfold expected from the difference in D content) for the N&#95;{2}D&#95;{2} versus D&#95;{2}-only fill suggest it is feasible to develop the platform for studying CNO-cycle-relevant nuclear reactions in a plasma environment.

Objective: To evaluate the clinical efficacy of posterior lumbar interbody fusion combined with Ponte osteotomy in the treatment of patients with degenerative scoliosis. Methods: The medical records and imaging data of degenerative scoliosis in department of orthopedics, Peking Union Medical College Hospital from 2013 to 2022 were retrospectively collected, and the shortest follow-up time was 1 year. A total of 38 patients were included, including 13 males and 25 females, aged 50-87(65.6±10.9) years old.The follow-up was12-119(43±20) months. Standing position full spine anteroposterior lateral X-ray examinations were performed on all patients preoperatively, postoperatively, and at latest follow-up. The length of hospital stay, complications, operation time, blood loss, instrumented segment, fusion segmen were recorded. The clinical scores and coronasagittal imaging indicators at three time points were compared. Results: The operation time was (274.5±70.5)min, and intraoperative blood loss was (619.2±93.5)ml. The coronal vertical axis was improved from (2.9±1.8)cm preoperatively to (1.2±1.0)cm postoperatively. The preoperative coronal Cobb angle was 16.6°±9.9° and the immediate postoperative correction was 6.4°±4.0°( t =-6.83, P <0.001). The difference was statistically significant ( t =-6.12, P <0.001). The coronal Cobb Angle at the last follow-up was 5.7°±3.7°, and there was no significant orthopaedic loss at the last follow-up ( t =-6.12, P <0.001).The sagittal vertical axis decreased from (5.6±3.9)cm preoperatively to (3.2±2.5) cm immediately after operation ( t =-6.83, P <0.001), and was well maintained at the last follow-up[(2.7±1.8) cm, t =-7.77, P <0.001]. Lumbar lordosis increased from 21.8°±10.2° preoperatively to 35.8°±8.3° postoperatively( t =12.01, P <0.001)and 40.1°±8.6° at last follow-up( t =-10.21, P <0.001). Oswestry disability score (ODI score), visual analogue score (VAS) low back pain score and VAS leg pain score were also lower after surgery than before surgery (all P <0.05). Conclusion: Posterior lumbar interbody fusion combined with Ponte osteotomy can significantly improve the coronal and sagittal plane deformity and postoperative functional score in adult patients with degenerative scoliosis.

Aim: To identify components of an online education intervention to improve preference for, and uptake of, long-acting reversible contraception in women from culturally and linguistically diverse backgrounds (CALD)., Issue Addressed: Women from culturally and linguistically diverse (CALD) backgrounds have greater rates of unintended pregnancies than those born locally and are less likely to use long-acting reversible contraceptives (LARCs), which are highly effective at reducing unintended pregnancy. Increasing the uptake of LARC in women from CALD backgrounds may reduce the burden of unintended pregnancy in this high-risk group. An online education intervention has been shown to be effective at increasing preference for and uptake of LARC in young women. We aimed to describe what women from CALD backgrounds thought were the potentially effective components of an online education intervention to increase preference for, and uptake of, long-acting reversible contraception., Methods: This qualitative study involved semi-structured interviews with six Australian English-speaking women from each of Chinese, Indian, and Middle Eastern cultural backgrounds. Women were recruited through targeted Facebook advertising. Data were analysed using Braun and Clarke thematic analysis., Results: A total of 18 participants were interviewed. We have demonstrated the importance of messages tailored to cultural values, translating the video, widening the target audience to both men and women and using specific social media platforms. For all women, the video needs to highlight the covertness of contraceptive methods, alongside stating cost and approach to access. For Indian women, the video needs to highlight the effect of LARC methods on the menstrual period for Indian women and include basic information on women's health. For Middle Eastern women the video should be explicit about LARC not equating to abortion and emphasise the low efficacy of natural contraceptive methods. For Chinese women, the video should address the misconception that hormones damage the body. Regarding delivery of the video, it should be translated and delivered by a female doctor from the same culture. For Chinese women, the video should include women from the same culture sharing anecdotes and use WeChat and Chinese schools as a platform for dissemination. For Middle Eastern and Indian women government websites should be used for dissemination. The video should be made available to all decision-makers in the reproductive planning process including male partners of Middle Eastern women, parents and peers of Chinese women, and for Indian women the male partner, family, and community leaders., Conclusions: There is a wide range of cultural adaptations that can be made to the online education videos about LARCs to improve uptake of LARCs and hence reduce the burden of unintended pregnancy in women from CALD grounds. SO WHAT?: Our findings will be used to modify an online education video about LARCs so that it is culturally appropriate for women from CALD backgrounds., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated. The bioassay results showed that compounds A 8 , A 13 , A 16 , B 1 , B 3 , B 4 , B 5 , B 10 , B 12 - 20 , C 3 , C 5 , C 9 , C 10 , C 14 , C 15 , C 17 and C 19 showed 100% activity at a concentration of 500 µg/mL against the Plutella xylostella (P. xylostella). Among them, B 15 which contains a thiadiazole sulfonate structure still shows 100% activity at 50 µg/mL concentration against P. xylostella and had the lowest median lethal concentration (LC 50 ) (7.61 µg/mL) among the target compounds. Further mechanism studies are conducted on compounds with better insecticidal activity. Molecular docking results shows that B 15 formed hydrophobic interactions π-π and hydrogen bonds with the indole ring of Trp532 and the carboxyl group of Asp384, respectively, with similar interaction distances or bond lengths as those of diflubenzuron. Moreover, chitinase inhibition assays are performed to further demonstrate its mode of action. In addition, the anti-bacterial activity of the series of compounds is also tested and the results showed that the series of compounds has moderate biological activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), with inhibition rates of 91%, 92% and 92%, 88% at the concentration of 100 µg/mL, respectively. Our study indicates that B 15 can be used as a novel insecticide for crop protection., (© 2024. The Author(s).)

Introduction: Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on improving anxiety and distress symptoms including nausea and vomiting in this vulnerable group. This trial aims to evaluate the effects of IVR intervention on anxiety, chemotherapy-induced nausea and vomiting and anticipatory nausea and vomiting in patients with paediatric cancer receiving first chemotherapy., Method and Analysis: An assessor-blinded, randomised controlled trial with a mixed methods evaluation approach. On the basis of our pilot results, 128 chemotherapy-naive patients with paediatric cancer scheduled to receive their first intravenous chemotherapy will be recruited from a public hospital and randomly allocated to intervention (n=64) or control groups (n=64). The intervention group will receive the IVR intervention for three sessions: 2 hours before the first chemotherapy, 5 min before and during their first chemotherapy and 5 min before and during their second chemotherapy, respectively. The control group will receive standard care only. A subsample of 30 participants in the intervention group will be invited for a qualitative interview. Study instruments are: (1) short form of the Chinese version of the State Anxiety Scale for Children, (2) visual analogue scale for anticipatory nausea and vomiting, (3) Chinese version of the Multinational Association of Supportive Care in Cancer Antiemesis Tool and (4) individual face-to-face semistructured interviews to explore intervention participants' perceptions of the IVR intervention., Ethics and Dissemination: This study has been approved by the Hong Kong Children's Hospital Research Ethics Committee (HKCH-REC-2021-009). The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations., Trial Registration Number: ChiCTR2100048732., Competing Interests: Competing interests: None declared., (© 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.)

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Introduction: Cannabis use has been associated with an increased incidence of psychiatric disorders, yet the underlying neurobiological processes mediating these associations are poorly understood. Whereas exposure to Δ9-tetrahydrocannabinol (THC) has been associated with the development or exacerbation of psychosis, treatment with cannabidiol (CBD) has been associated with amelioration of psychosis. In this study, we demonstrate a complex effect of CBD in mouse models of psychosis, based on factors, including dose, strain, and genotype. Methods: Adult GluN1 knockdown (GluN1KD) and dopamine transporter knockout (DATKO) mice (almost equally balanced for male/female) were acutely treated with vehicle, THC (4 mg/kg), CBD (60, 120 mg/kg), or THC:CBD (1:15, 4:60 mg/kg) and tested in behavioral assays. Results: GluN1KD and DATKO mice displayed hyperactivity, impaired habituation, and sensorimotor gating, along with increased stereotypy and vertical activity. THC, alone and in combination with CBD, produced a robust "dampening" effect on the exploratory behavior regardless of strain or genotype. CBD exhibited a more complex profile. At 60 mg/kg, CBD had minimal effects on horizontal activity, but the effects varied in terms of directionality (increase vs. decrease) in other parameters; effects on stereotypic behaviors differ by genotype, while effects on vertical exploration differ by strain×genotype. CBD at 120 mg/kg had a "dampening" effect on exploration overall, except in GluN1KD mice, where no effect was observed. In terms of sensorimotor gating, both THC and CBD had minimal effects, except for 120 mg/kg CBD, which exacerbated the acoustic startle response. Conclusions: Here, we present a study that highlights the complex mechanism of phytocannabinoids, particularly CBD, in models of psychosis-like behavior. These data require careful interpretation, as agonism of the cannabinoid receptor 1 (CB 1 ) resulting in a decrease in locomotion can be misinterpreted as "antipsychotic-like" activity in murine behavioral outputs of psychosis. Importantly, the THC-mediated decrease in hyperexploratory behavior observed in our models (alone or in combination) was not specific to the genetic mutants, but rather was observed regardless of strain or genotype. Furthermore, CBD treatment, when comparing mutants with their wild-type littermate controls, showed little to no "antipsychotic-like" activity in our models. Therefore, it is not only important to consider dose when designing/interpreting therapeutically driven phytocannabinoid studies, but also effects of strain or genetic vulnerability respective to the general population.

A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1 + rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL., (© 2023. The Author(s).)

Objective: To compare and contrast the perceived care needs of children with life-limiting conditions (CLLC) from the perspectives of the children, parents and healthcare providers., Design: A qualitative case study method using semistructured interviews was employed with a within-case and across-case analysis. Themes and subthemes emerging from the cases were compared and contrasted in the across-case analysis to explore the similarities and variations in participant perceptions., Setting/participants: The setting was the paediatric departments of five regional hospitals in Hong Kong. Twenty-five sets of informants (CLLC-parent-healthcare provider) were recruited, with 65 individual interviews conducted., Results: A total of 3784 units of analysis were identified, resulting in three themes with subthemes. 'Living with the disease' (55.8%) occupied the largest proportion, followed by 'information and understanding about the disease' (27.4%), and 'care support and palliative care' (16.8%). Healthcare provider support mainly focused on physical concerns. Family and social support were present, but carer stress created tension between couples. Doctors were the primary source of medical information, but the parents had to seek further information via the internet and support from patient groups. There was a perceived need for better coordination and collaboration of care. The palliative care approach coordinated by nurses was seen as helpful in addressing the care needs of the CLLC., Conclusions: This original study identified the importance of palliative care with active engagement of parents which can address the service gap for CLLC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Magnetic reconnection is a ubiquitous and fundamental process in plasmas by which magnetic fields change their topology and release magnetic energy. Despite decades of research, the physics governing the reconnection process in many parameter regimes remains controversial. Contemporary reconnection theories predict that long, narrow current sheets are susceptible to the tearing instability and split into isolated magnetic islands (or plasmoids), resulting in an enhanced reconnection rate. While several experimental observations of plasmoids in the regime of low-to-intermediate β (where β is the ratio of plasma thermal pressure to magnetic pressure) have been made, there is a relative lack of experimental evidence for plasmoids in the high-β reconnection environments which are typical in many space and astrophysical contexts. Here, we report strong experimental evidence for plasmoid formation in laser-driven high-β reconnection experiments.

Purpose: Adolescent and young adult (AYA) patients with cancer often experience unique physical and psychosocial complications. They may turn to traditional, complementary and integrative medicines (TCIM) to address these concerns. To examine the pattern of TCIM use among AYA patients with cancer and explored their preferences regarding TCIM education., Methods: Between August 2021 and December 2022, 246 patients diagnosed with cancer between 15 and 39 years old were recruited from hospitals in Hong Kong. They completed a structured questionnaire on TCIM use, symptom burden, psychological status and preference on education content. Multivariable logistic regression was used to identify predictors of TCIM use, adjusting for age and sex., Results: Overall, 60.2% reported TCIM use, most commonly vitamins (24.0%) and Chinese herbal medicine (22.0%). The most common reasons for using TCIM were to improve general health (70.9%) and manage chronic symptoms (33.1%). Among patients on active treatment, TCIM users tend to report higher anxiety symptoms (aOR = 1.13, 95% CI = 1.02-1.27). TCIM users who were post-treatment were more likely to have chronic comorbidities (aOR = 3.54, 95% CI = 1.29-11.5). AYA patients indicated that they would like TCIM information to address specific needs, particularly fatigue (53.7%) and psychological problems (54.1%)., Conclusions: The use of TCIM is common among AYA patients with cancer, especially among patients with high symptom burdens. A tailored education programme should be provided based on patients' preferences and needs. Healthcare professionals including oncologists and oncology nurses should communicate with AYA patients about TCIM use and address their needs by making evidence-based referrals/recommendations based on treatment status and symptom burden., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)