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Non-radiative quantitation of NIS-dependent iodine accumulation in cells using single-cell inductively coupled plasma mass spectrometry
Get PDFIodine is an essential trace element, and its deficiency continues to pose a significant global health burden. Reliable biomarkers such as urinary iodine concentration (UIC), thyroglobulin, thyroid volume, and breast milk iodine levels are well-established for assessing individual and population iodine status. However, mechanistic studies into iodine metabolism and distribution remain limited by the use of the radionuclide iodine-131 which imposes practical limitations on experimental design, cost, and safety. While mass spectrometry offers a sensitive, non-radiative alternative, conventional methods often require complete tissue digestion, thereby eliminating spatial or cell-level information. In this proof-of-concept study, we demonstrate the feasibility of single-cell inductively coupled plasma mass spectrometry (scICP-MS) for quantifying iodine at the single-cell level. Iodine accumulation in TPC-1 human papillary thyroid carcinoma cells stably expressing the sodium iodine symporter (NIS) is shown to not only be greater than in parental TPC-1 cells but is also markedly broader and has a positively skewed distribution across the cell population. Such population-level insight would have been lost by conventional bulk analysis, clearly demonstrating the advantage of a single-cell approach. After removal of iodine-containing medium, cells stably expressing NIS sustain a greater intracellular iodine concentration than the parental cell line (longer iodine biological half-life: TPC-1 = 1.9 min, TPC-1-NIS = 8.3 min) which we suggest is a consequence of the dynamic equilibrium between iodine efflux and re-uptake of exported iodine via NIS within the closed system
The catalytic activity of Ca/Fe-rich incineration ash in the pyrolysis of epidemic wood
No full textThe spread of pine nematode disease caused by epidemic wood poses a great challenge to the environment, and there is an urgent need to develop effective processing methods; however, Ca/Fe-rich sludge ash can improve the pyrolysis properties of biomass. Therefore, this paper focuses on the pyrolysis mechanism of epidemic wood with the addition of Ca/Fe-rich sludge ash. The presence of Ca-rich sludge ash was found to extend the pyrolytic temperature window of epidemic wood, intensify the cracking of its volatile constituents, and extend its reaction duration. At the same time, the Ca-rich sludge reduces the pyrolysis activation energy to 152.39 kJ/mol. The Fe-rich sludge ash demonstrated the capacity to lower the energy barriers during the initial phase of pyrolysis. Concurrently, the Ca-rich sludge ash accelerated the dehydration reaction of the epidemic wood, leading to 21.02% and 30.69% increases in the contents of acids and ketones in the pyrolytic oil, respectively. The Fe-rich sludge ash contributed to a notable 14.52% increase in aromatic compounds in the oil and a 19.14% decrease in alcoholic compounds. Additionally, the Ca-rich sludge ash accelerated the decomposition of lipid organic matter at elevated temperatures, enriching the pyrolytic char with more unsaturated bonds. This research lays a theoretical foundation for the safe and efficacious thermal decomposition of epidemic wood, thereby enhancing its utilization within the forestry industry.</p
Effectiveness of Psychosocial Interventions for Adults With Substance Use Disorder That Have a Co-Occurring Common Mental Health Disorder:An Umbrella Review
Get PDFIssues: People with substance use disorders can have co‐occurring mental disorders. Approach: An umbrella review was conducted to identify evidence of the effectiveness of psychosocial interventions for adults (aged 18+) with substance use disorders and co‐occurring common mental health disorders. Systematic reviews were sought of randomised controlled trials of psychosocial interventions compared to each other, treatment as usual or wait‐list. Five databases were systematically searched in February 2024. Data, including critical appraisal (Joanna Briggs Institute Checklist), were extracted by one reviewer and checked by another. Data were discussed in a narrative review. Key Findings: Of 5420 unique records, 28 systematic reviews were included. The methodological quality of the reviews was good. Most reviews focused on depression, anxiety or post‐traumatic stress disorder. There was much heterogeneity between reviews, and randomised controlled trials within reviews. Most of the interventions and many of the treatment‐as‐usual comparators resulted in significant improvement in substance use and mental health disorders. Results suggested integrated (co‐ordinated) treatment for co‐occurring diagnosis patients was better than treating one condition alone, and usually better than parallel uncoordinated services. There was limited evidence assessing sequential treatment, but this suggested similar effectiveness to integrated treatment. Implications: Implications for current practise could not be recommended due to heterogeneity. Improvement shown by all types of psychosocial intervention including active comparators precluded recommending one type of intervention over another. Conclusion: Further research is needed comparing integrated with parallel or sequential treatment, with follow‐up of 6 months or longer, and sample size large enough to encompass dropout
Constitutional Identity and States of Exception
No full textThis chapter argues that this notion of an ‘idealized or manufactured homogeneity’ present in theories of constitutional identity provides the basis for a comparative conceptual analysis between constitutional identity and states of exception, in particular, the understanding of states of exception articulated by Carl Schmitt. By understanding constitutional identity through this lens of exception, the utility of constitutional identity can be revealed, but also, importantly, its fundamental dangers; not least, the fundamental democratic principles that ought to be embodied in a liberal constitutionalist order. However, constitutional identity’s other function as a means of delineating the limits of the constitutional amendment power also reveals its potent potential to limit constitutional abuse, not least in the context of abuse of emergency powers
International Consensus-Driven Recommendations for Patient-Reported Outcome Research Objectives in Early Phase Dose-Finding Oncology Trials:OPTIMISE-ROR
No full textPurposeThere is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.MethodsUsing the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion.ResultsConsensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies.ConclusionThis foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation—ultimately contributing to the development of safer, more effective therapies
From definitions to implementation – A guide to collect and apply the Lancet Commission on Global Surgery indicators:An Utstein consensus report
No full textMetrics for surgery, obstetrics, and anesthesia are crucial for implementing programs and monitoring progress toward safe and effective healthcare systems in pursuit of universal healthcare. A suite of metrics put forward by the Lancet Commission on Global Surgery has been adopted in principle by global health, anaesthesia, and surgical leadership in diverse settings. However, barriers to implementation limit their value. Barriers include inconsistencies in definitions and methodologies such as inadequate consideration given to sampling frames, representativeness, categorizations, missing data, and data collection infrastructure. Using the Utstein consensus methodology, we developed a uniform approach to collecting metrics in surgery, obstetrics, and anesthesia. We created a standard toolkit to facilitate the rapid implementation of the Lancet Commission indicators. The metadata and data dictionaries allow a standardized assessment of preparedness for, delivery of, and the effect of care at the population level
Tackling energy poverty in Europe through energy communities:tracing the innovation journeys to support an emerging niche
Get PDFEnergy poverty (EP) is an obdurate and significant problem across Europe, worsened in recent years by rising living costs, escalating energy prices and intensifying global geopolitical tensions. While government initiatives are patchy and insufficient for the scale of the problem, novel actor configurations and innovative approaches are needed to address the issues. Energy Communities (ECs), who are diverse in structure and founding objectives, are increasingly expected by European policy to alleviate EP; however, how they can or do innovate to do so is poorly understood, which hinders the development of appropriate support for them to be effective. This paper, drawing on qualitative and quantitative data from 77 ECs in 14 European countries, with 6 in-depth case studies, examines innovation journeys of ECs in addressing EP in their wider communities. By applying the concept of social innovations (SIs), we identify key types of innovation and how they emerge within ECs. We understand SIs as new ways of thinking and understanding, organising and implementing EP alleviation action. We further examine the networks and actor configurations that facilitate these processes, assessing the extent to which SIs transcend the local context. Through observed knowledge exchange, we identify an emerging energy poverty alleviation niche within the now well-established EC niche. From this new understanding of social innovation processes and niche emergence in ECs, we make recommendations for European and national policies to enable ECs as actors in EP alleviation across Europe, leveraging their ability to form social relationships with hard-to-reach households
Health disparities in transitions between kidney replacement therapy modalities and mortality in England:A multistate model using UK Renal Registry data
Get PDFBackground: While ethnic and deprivation-related disparities in kidney replacement therapy (KRT) initiation are well established, their impact on transitions between treatment modalities and mortality over the course of kidney failure remains poorly understood. This study aimed to examine the association between ethnicity and area-level deprivation and the rates of transition between treatment modalities and death across the patient life course on KRT. Methods and findings: We used a parametric multistate model to analyse UK Renal Registry data from 93,451 patients initiating KRT in England between 2005 and 2020 with a median follow-up of 1,497 days [IQR: 640−2,841] (4.1 years [IQR: 1.75,7.8]). We estimated transition-specific hazard rates and probabilities between peritoneal dialysis (PD), home haemodialysis (HHD), in-centre haemodialysis (ICHD), transplantation, and death using Weibull proportional hazard models. Ethnicity and area-level deprivation (measured by quintiles of the Index of Multiple Deprivation [IMD]) were included as covariates of primary interest, with models additionally adjusted for sex, age and diabetes mellitus as the primary kidney disease (PKD). Compared with White patients, Asian patients had lower transition rates from ICHD to PD (hazard ratio [HR]: 0.68, 95% confidence interval [CI] [0.51,0.91]), and from PD to ICHD (HR 0.85, 95% CI [0.78,0.92]), but a higher rate of returning to ICHD after transplantation (HR 1.12, 95% CI [1.01,1.24]). Black patients also had lower transition rates from ICHD to PD (HR 0.64, 95% CI [0.47,0.88]) and to HHD (HR 0.47, 95% CI [0.37,0.61]), but higher rates of transition from PD to ICHD (HR 1.16, 95% CI [1.01,1.33]) and from transplantation to ICHD (HR 1.73, 95% CI [1.44,2.08]). Patients living in the most deprived areas had lower transition rates from ICHD to PD (HR 0.63, 95% CI [0.56,0.70]), to HHD (HR 0.49, 95% CI [0.38,0.64]), and to transplantation (HR 0.57, 95% CI [0.52,0.64]), and higher rates from transplantation to ICHD (HR 1.63, 95% CI [1.43,1.85]) and to death (HR 1.53, 95% CI [1.33,1.76]), compared with those from the least deprived areas. A limitation of our study is that, apart from diabetes mellitus as the PKD, comorbidities were not included in the analysis due to incomplete reporting in the UK Renal Registry. This should be considered when interpreting the observed disparities, particularly those related to area-level deprivation. Conclusions: These findings highlight persistent inequalities throughout the KRT pathway. The multistate modelling framework applied in this study offers a foundation for future research to design and evaluate interventions that improve equity and patient outcomes in kidney care
Sexual function and wellbeing of women using modern contraceptive methods in Rwanda:a multicenter cross-sectional study
Get PDFBackground: Family planning (FP) is essential for sustainable development, maternal health, and women's reproductive well-being. Despite its critical role, Rwanda continues to experience a highly unmet need for FP. Women's experiences and perceptions of contraceptive methods can significantly affect their adoption and use. This study aimed to assess the sexual function and well-being of women using modern FP methods in Rwanda.Methodology: A multicenter cross-sectional study involving 415 women aged ≥18 years who had used a modern FP method for at least ≥6 months was conducted across three urban and two rural FP clinics in Rwanda. Sexual function and well-being were evaluated via the Female Sexual Distress Scale-Revised (FSDS-R), with scores <11 indicating good sexual function. Utilizing R programming version 4.0.2, Logistic regression was used to examine associations between demographic/clinical factors and sexual distress.Results: Overall, 79.5% of women had good sexual function (FSDS-R < 11). Copper intrauterine device (IUD) users (96%) and those with permanent sterilization (84%) reported the highest sexual satisfaction. In multivariable analysis, underweight women (BMI <18.5) had 3.08-fold higher odds of sexual distress than normal-weight women (OR = 3.08; 95% CI 1.10–8.69). Conversely, IUD users had 86% lower odds of distress than implant users (OR = 0.14; 95% CI 0.03–0.42). Other factors, such as education level, were not significantly associated after adjustment.Conclusion: The majority of Rwandan FP users in this study reported satisfactory sexual function. Contraceptive method and BMI were key predictors. These findings underscore the importance of integrating sexual health counseling into FP programs to reassure women about contraceptive side effects and support informed method choices that optimize reproductive well-being
Bora bridges Aurora-A activation and substrate recognition of PLK1
Get PDFThe activation of PLK1 in late G2 is critical for mitotic entry, requiring its phosphorylation by Aurora-A, facilitated by the intrinsically disordered protein Bora. The structural basis of this mechanism has remained unresolved. Here, we present models of the Aurora-A/Bora complex and the Aurora-A/Bora/PLK1 complex, validated with site-specific mutagenesis, biochemical assays and NMR spectroscopy. Bora wraps around the N-lobe of Aurora-A, occupying the pockets used by its other activators. A CDK1 phosphorylation site on Bora (Ser112) mimics the structural role of Aurora-A activation loop phosphorylation within a TPX2-like binding motif. In the ternary complex, Bora bridges the two kinases, orienting the activation loop of PLK1 towards the active site of Aurora-A. Bora residues 56–66 form a critical interface with a conserved pocket on the PLK1 C-helix that is analogous to the TPX2-binding Y-pocket of Aurora-A. Aurora-A phosphorylation of Bora Ser59 creates an additional interaction that increases the efficiency of PLK1 phosphorylation. These findings deepen our understanding of Aurora-A regulation by its disordered binding partners and establish a mechanistic framework for Bora-dependent activation of PLK1
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