There is a paucity of research that considers personal factors that have recently been shown to be important to those who use cochlear implants (CI). This study aimed to develop the Living with Cochlear Implants (LivCI) questionnaire, a patient-reported outcome measure (PROM) of personal factors important to living with cochlear implants, and evaluate its psychometric properties using Rasch and classical test theory (CTT) analyses. Multi-phase, prospective observational design. CI candidates and recipients (n = 267) completed a 54-item draft LivCI. The item pool was assessed for Rasch model fit, including overall scale and item fit, local dependency, rating scale functioning, differential item functioning (DIF), reliability and unidimensionality. Results guided iterative refinements to produce a definitive LivCI. LivCI scales were evaluated in a second sample (n = 145) using CTT for internal consistency reliability (Cronbach's alpha) and criterion and construct validity. A hypothesis testing approach, comparing LivCI scores with participants' scores on five comparator PROMs, was used. We constructed a 22-item version of the LivCI comprising four unidimensional subscales: (1) function and participation; 2) psychosocial and wellbeing; 3) stigma; and 4) device aesthetics and management. Scales represented domains of a co-developed conceptual framework. All met the Rasch model requirements of fit, unidimensionality, local item independence and item invariance for age and gender (DIF), except the Device Aesthetics and Management scale with one dependent item pair. A 4-point response category structure was adopted to address threshold disordering. Person separation reliability (range = 0.57 to 0.85) and internal consistency reliability (Cronbach's [Formula: see text] = 0.64 to 0.94) were acceptable with exception of the Device Aesthetics and Management Scale. The LivCI was highly correlated (r > 0.6) with PROMs considered to measure similar constructs, sufficient evidence of criterion validity (Pearson correlation value range = 0.62 to 0.75, 100% of a priori hypotheses met). Construct validity was partially supported with 54% (15/28) of predefined hypotheses confirmed. The 22-item LivCI, comprising four standalone scales, met Rasch model requirements for unidimensionality, invariance, local independence and item fit. With further validation, the LivCI has potential for implementation in routine care and as a research tool. (350 words).
The 48th Annual Meeting and International Conference of the Environmental Mutagen Society of India (EMSI) on 'Environmental Mutagenesis & Epigenomics in Relation to Human Health' was held at Jamshedpur Co-Operative College, in association with Kolhan University, Jharkhand, India, from January 29-31, 2026. There were 141 deliberations in total, with participation from researchers, academicians, Vice-Chancellors, and state government officials from India and eight other countries. The scientific topics, including environmental impact on humans and aquaculture, transgenerational plant protection, molecular insights into cancer research, plants with antimutagenic potential, and sustainable agriculture through the use of bio-pesticides and bio-fertilizers, broadly justified the conference theme. The molecular mechanisms of pathogenesis were discussed through lectures on signalling pathways, gene expression, and DNA damage and repair, highlighting targeted drug development. Additionally, in silico docking of synthetic drugs and nanoparticles was discussed in detail. Notably, nanotoxicology, microplastics, airborne particulate matter, and prenatal arsenic exposure were shown to have a significant impact on human health. As Jharkhand and neighbouring states depend largely on agricultural yield, discussions on the use of plant-based medicines, harnessing infection and immunity, and agricultural eco-toxicology suggested ways to protect farmers' health and the food chain from the overuse of chemicals. Altogether, the deliberations supported several Sustainable Development Goals and highlighted cost-effective agricultural modalities. These messages were disseminated to the public through local media via daily briefings. Notably, this EMSI conference provided a platform for scientific exchange that attracted administrators and pollution control regulators aimed at protecting human health by mitigating environmental exposure.
In August 2024, mpox was declared a public health emergency. However, little is known about how the proteins of the mpox virus (MPXV) interact with host innate immunity. This study identified that the D8L protein of MPXV inhibited the interferon (IFN)-mediated antiviral innate immune response and suppressed the mRNA transcription and protein expression of several IFN-stimulated genes, including Cig5, MX2, ISG56, IFITM1, OAS1, and ISG15. Mechanistically, D8L prevented antiviral immune responses by interacting with signal transducer and activator of transcription 1 (STAT1). Furthermore, D8L interacted with the SH2 structural domain of the STAT1 protein but not with other regions. The point-mutant plasmids capable of binding STAT1 were D8L-9-11, D8L-13, and D8L-18. In addition, D8L attenuated IFN responses by inhibiting the phosphorylation and nuclear translocation of STAT1. These findings provide valuable information for the development of novel antiviral therapies.
Learning health systems (LHSs) aim to integrate continuous learning into routine care, yet their development raises persistent ethical challenges. Questions remain about when and how informed consent should be obtained, how ethical oversight should be organized for learning activities that blur the boundary between care and research, and what system-level conditions are necessary to support ethically sound learning. This integrative review synthesizes ethical recommendations for the design, implementation and evaluation of LHSs, and aims to provide practical guidance and identify gaps in the current literature. A systematic search of PubMed, Web of Science and a search on LinkedIn on 22 October 2025 identified studies offering explicit ethical recommendations related to LHSs. Eligible studies were situated within an existing LHS and provided at least one actionable ethical recommendation. Data were extracted and analysed using Friedman's LHS functioning cycle of three knowledge-to-action steps: data to knowledge, knowledge to practice and practice to data. In total, 44 studies met the inclusion criteria. Ethical guidance was unevenly distributed across Friedman's cycle. Most studies (n = 32) focused on transforming data into knowledge, addressing data governance, patient autonomy, consent models and ethical prerequisites for artificial intelligence (AI). Far fewer studies (n = 6) examined translating knowledge into practice, where attention centred on the ethical implementation of AI, workflow integration and risk mitigation. The final step, feeding performance back into new data, was represented (n = 6), with limited guidance on accountability, continuous monitoring and equitable interpretation of performance outcomes. Across all stages, informed consent and ethical oversight emerged as dominant themes, though considerable variation existed in how institutions operationalized these concepts. Current ethical discourse in LHSs remains focused mainly on transforming data to knowledge. Relatively limited recommendations for ethical implementation of other action steps were identified. In addition, some of the recommendations contradicted each other or offered differing advice on aspects of the ethical implementation of LHS (for instance, on informed consent and ethical review). This imbalance highlights the need for context-sensitive governance models, empirical evaluation of ethical practices in real-world LHSs and regulatory frameworks that reflect the dynamic nature of continuous learning.
In Southwest China, the spring-colored leaves of the Lauraceae plant Litsea coreana, often known as hawk tea, produce a traditional beverage with cultural and economic significance. Its immature leaves are generally red or green coloration, transitioning to common green as they mature. The possible quality benefits of high-anthocyanin tea cultivars with unusual leaf hues have recently drawn attention. It is important from a scientific and practical standpoint to clarify the metabolism and manufacture of pigments in hawk tea leaves that have different starting hues during the developmental stages. This study applied both targeted metabolomics and transcriptomics to investigate the metabolite accumulation and molecular mechanisms in red and green hawk tea tender leaves across three developmental stages. Metabolomic profiling revealed that cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, and pelargonidin-3-O-glucoside specifically accumulated in red tender leaves (2.44 to 4.59 Log2FC higher than in green leaves), with levels progressively decreasing during the red-to-green transition. Transcriptomic analysis demonstrated that key late biosynthetic genes (ANR, 3GT) were consistently upregulated in red leaves and strongly correlated with anthocyanin content. In contrast, lignin pathway genes (HCT, CCOAMT) were downregulated in red leaves, suggesting that carbon flux is preferentially directed toward anthocyanin rather than lignin synthesis in red leaves. Additionally, co-expression network analysis further delineated nine candidate transcription factors (three MYB, two bHLH, three C2C2 zinc finger proteins, and one GRAS) that exhibited coordinated expression patterns with pigment biosynthetic genes, were predicted to directly or indirectly regulate anthocyanin biosynthesis in response to endogenous substances such as nitrogen, hormones, and sugars. Our findings identify that red leaf color in L. coreana is driven by anthocyanin accumulation, which is achieved through a metabolic shift that directs carbon flux away from lignin and toward anthocyanin biosynthesis. This shift is likely regulated by a set of nine transcription factors. These findings provide concrete targets for breeding high-anthocyanin hawk tea varieties.
High sustained virological response (SVR) was achieved after direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C viral (HCV) infection. Nevertheless, the factors predicting hepatocellular carcinoma (HCC) and liver-related complications (LRC) following SVR are required. HCV-infected patients who received DAA and achieved SVR at King Chulalongkorn Memorial Hospital, Thailand during 2011 and 2021 were enrolled. Liver stiffness was measured by transient elastography (TE), AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) scores, were collected at pre-treatment and within 12 months after SVR. Cox proportional hazard model assessed predictors of HCC and LRC. A total of 355 participants were enrolled. During the median follow-up period of 27 months, 15 (4.2%) and 24 (6.8%) developed HCC and LRC. Baseline TE showed the highest AUROC of 0.82 and predicted HCC with an adjusted hazard ratio (aHR) of 1.03 [95% confidence interval (CI) 1.00-1.09]. Baseline TE ≥ 13 kPa was associated with LRC with aHR of 3.28 (95%CI 1.17-9.19). In a subgroup analysis of 168 patients with post-treatment liver stiffness, the TE, APRI, and FIB-4 after SVR significantly declined. In the multivariate analysis, only TE ≥ 13 kPa after SVR anticipated HCC and LRC with aHR of 7.75 (95%CI 1.62-37.20) and 3.36 (95%CI 1.09-10.38). Baseline TE independently predicted HCC and LRC in HCV-infected patients with SVR after DAA therapy. In the subgroup analysis, liver fibrosis regression was observed after SVR. Additionally, post-treatment TE might more reliably anticipate adverse outcomes than pre-treatment values.
Early postoperative cerebral infarction (EPCI) remains a major complication following surgical treatment of aneurysmal subarachnoid hemorrhage (aSAH) and contributes to unfavorable neurological outcomes. The neutrophil-to-apolipoprotein A1 ratio (NAR), which indicates systemic inflammation and lipid-related vascular protection, has shown prognostic significance in multiple vascular diseases. However, its clinical value in identifying patients at risk of EPCI after aSAH remains unclear. This retrospective study included 517 patients with aSAH who underwent surgical treatment. Patients were divided into four groups according to the quartiles of their admission NAR. The relationship between NAR and EPCI was investigated using multivariable logistic regression, receiver operating characteristic curve analysis, restricted cubic spline modeling, subgroup analyses, and propensity score matching. Of the 517 patients included, 90 (17.41%) developed EPCI. Higher NAR levels were associated with increased clinical and radiological severity, including higher Hunt-Hess and modified Fisher grades, as well as a significantly increased risk of EPCI. NAR was independently linked to EPCI after controlling for confounders (adjusted odds ratio = 1.16; 95% CI: 1.09-1.24; P < 0.001). aSAH patients in the highest quartile exhibited a 2.68-fold higher risk of EPCI compared to those in the lowest quartile. Receiver operating characteristic curve analysis indicated that NAR had moderate discriminative ability for EPCI, with an area under the curve of 0.698. Restricted cubic spline analysis demonstrated a positive dose-response association. These findings were consistent across subgroup analyses and were further corroborated by propensity score matching. Higher admission NAR independently correlated with an increased risk of post-operative EPCI and unfavourable prognosis. NAR, as an affordable and readily accessible biomarker, could offer practical benefits for early risk assessment and perioperative clinical management.
Excessive hepatic glucose production is a key driver of the progression of type 2 diabetes (T2DM), a highly prevalent global metabolic disorder. We previously reported that Sam68 expression is upregulated in the livers of both diabetic patients and mouse models, and hepatocyte-specific knockdown of Sam68 greatly alleviates hyperglycemia and improves insulin sensitivity in diabetic mice. Here, we engineered a series of ligand-functionalized lipid nanoparticles (LNPs) and identified a galactose-decorated formulation (LNP-Gal) that enables efficient hepatocyte-selective delivery of Sam68 siRNA, thereby achieving robust Sam68 silencing and suppressing hepatic gluconeogenesis in both cellular and animal models. In both genetic and diet-induced diabetic mouse models, systemic administration of siSam68/LNP-Gal improved glycemic control and insulin responsiveness and attenuated hepatic gluconeogenic output, accompanied by suppression of the hepatic gluconeogenic program. Thus, we establish siSam68/LNP-Gal as a hepatocyte-selective siRNA delivery system that elicits a potent antihyperglycemic effect with a favorable safety profile in vitro and in vivo, providing a promising siRNA-based strategy for the treatment of T2DM and related metabolic disorders.
Antimicrobial resistance (AMR) is largely attributable to inappropriate antibiotic use particularly in low-and-middle-income countries (LMICs). Misidentification of antibiotics could contribute to inappropriate use, as people may use the wrong drugs for their conditions. Misidentification and inappropriate use are worsened by self medication and easy access to antibiotics that are obtained from unapproved sources, including over-the-counter medicine sellers. This study explored community perceptions of confusion with antibiotics identification and pathways to improve the identification through physical or visual appearance. A qualitative exploratory study was conducted from June 2021 and December 2022. A total of 140 In-depth interviews (IDIs) with medicine suppliers and 76 focus group discussions (FGDs) with community members were conducted in six countries spanning Africa (Ghana, Mozambique, South Africa) and Asia (Bangladesh, Thailand, Vietnam). Data was thematically analysed, and results presented as narratives with excerpts to support the findings. Identification of antibiotics through physical and visual appearance emerged as a complex issue influenced by a variety of factors including colours, shapes, sizes, packaging, local terminologies, and cultural beliefs. Visual cues serve as a primary means of antibiotic identification across all studied countries. This is especially significant in contexts where language barriers or low literacy hinder identification by written labels. While there are common trends across the studied countries, such as the importance of colour in identification, there are also significant regional and local variations that should be considered. The study highlights visual cues a primary means of antibiotic identification, providing valuable insights for developing targeted health literacy and antibiotic awareness interventions. Ultimately, enhancing the ability of community members to accurately identify antibiotics is a key step in promoting responsible antibiotic use practices and improving global health outcomes.
Loneliness during pregnancy is a critical yet overlooked determinant of maternal health, distinct from postpartum depression. While the COVID-19 pandemic highlighted this vulnerability, the mechanisms and typologies of prenatal loneliness remain under-researched. A scoping review was conducted following PRISMA-ScR guidelines. Seven databases were searched up to March 15, 2025. Influencing factors were first screened according to the Social-Ecological Model (SEM) framework, followed by thematic analysis. Twenty-three studies were included. Alongside emotional and social loneliness, a context-specific form tied to role transition during matrescence was identified ('transitional loneliness'). The reported prevalence of loneliness varied substantially, ranging from 26.26% to 55.40%. This wide variation likely reflects methodological heterogeneity (e.g., sampling and assessment tools) and population characteristics. Determinants were categorized into individual, interpersonal, community, and societal levels. Current generic instruments fail to capture the unique transitional nature of prenatal loneliness. Addressing this issue requires developing pregnancy-specific assessment tools and implementing multi-level interventions targeting multi-level socio-ecological factors.
This study aimed to develop and validate a prognostic model integrating hematoma (R1), perilesional (R2), and clinical features to predict 90-day outcomes. A total of 759 ICH patients from two centers were enrolled and allocated to training, internal validation, and external test sets. The primary endpoint was a poor 90-day outcome, defined as a modified Rankin Scale (mRS) score > 3. Independent clinical risk factors were identified via univariate and multivariate logistic regression analyses. Subsequently, seven prognostic models were constructed using R1, R2, clinical features, and their combinations. Model discrimination was compared using the DeLong test for the Area Under the Curve (AUC). Calibration and clinical utility were evaluated using calibration curves and Decision Curve Analysis (DCA). Multivariate analysis identified four independent risk factors for poor outcome: hematoma volume (OR 1.042; 95% CI 1.025-1.058; p < 0.001), mean hematoma density (OR 0.916; 95% CI 0.863-0.973; p = 0.004), age (OR 1.078; 95% CI 1.054-1.103; p < 0.001), and admission Glasgow Coma Scale (GCS) score (OR 0.777; 95% CI 0.708-0.853; p < 0.001). Among the seven models constructed, the tri-combined model (R1 + R2+Clinical) demonstrated the most stable and relatively better performance across all datasets, with an AUC of 0.791 (95% CI: 0.716-0.867) in the external test set. This model exhibited good calibration and favorable statistical net benefit on DCA. The integrated prognostic model combining hematoma and perilesional radiomic features with clinical data provides stable and incremental prognostic value for 90-day functional outcomes in patients with ICH.
The utility of antiretroviral therapy (ART) in the management of human immunodeficiency virus (HIV) is being challenged by growing HIV drug resistance (HIVDR). Although simulation modelling is useful for understanding complex problems, the extent to which it is used in HIVDR is unknown. This review aimed to determine how modelling has been used to inform HIVDR interventions and how its use can align with the World Health Organization (WHO) Global Action Plan (GAP) for HIVDR 2017-2021. This review involved a literature search across PubMed, Scopus, Web of Science, and Embase databases. Articles published after the introduction of ART, 1997 to 28th November 2025, were considered. Relevant information, including metadata, model descriptions, interventions, and their outcomes, was extracted. Findings from included papers were categorized according to their area of focus within the five strategic objectives of the WHO GAP for HIVDR 2017-2021. A total of 2346 articles were screened, and 17 articles were included in the final analysis. Most studies modelled HIVDR in sub-Saharan Africa (n = 13). Acquired resistance (n = 15) was assessed in most of the studies, followed by transmitted resistance (n = 7) and pretreatment resistance (n = 3). Most of the models were stochastic models(n = 11), with about one third of them analyzing cost effectiveness(n = 6). Ten models focused on the WHO GAP HIVDR strategic objective of prevention and response, four aligned with the objective of monitoring and surveillance, while the remaining three assessed a combination of the two objectives. None of the models assessed the remaining three objectives: research and innovation, laboratory capacity, or governance and enabling mechanisms. This review identifies a need for more cross-cutting analyses of multiple strategic objectives for HIVDR, including system-wide models to provide holistic insights into the complexity surrounding HIVDR. Employing patient and public involvement (PPI) in model development and intervention design would further strengthen model validity and transition to real-world settings (PROSPERO ID: CRD42024553557).
Frailty significantly complicates clinical outcomes in older adults with acute myocardial infarction, yet its progression is dynamic and heterogeneous. This study aimed to identify distinct frailty trajectory patterns and their predictors using a machine learning approach, to support evidence-based nursing interventions. A prospective cohort study was conducted, enrolling 583 older adults with acute myocardial infarction hospitalized between March 2023 and March 2024. We collected multidimensional clinical, physiological, psychological, and functional data at six time points over a one-year follow-up period. A patient similarity network was constructed from these longitudinal data, and the Structural Entropy Clustering algorithm was employed to identify frailty trajectory groups. Group differences were analyzed using ANOVA and Tukey's post hoc tests, while multinomial logistic regression was used to determine key predictors of trajectory membership. Four distinct frailty trajectories were identified: "Rapidly Worsening Frailty" ([Formula: see text], 13.4%), "Stable Non-Frail" ([Formula: see text], 44.7%), "Slowly Progressive Frailty" ([Formula: see text], 37.4%), and "Improving Frailty" ([Formula: see text], 4.5%). Significant differences were observed among the groups in functional status, psychological scores, nutritional status, left ventricular ejection fraction, and Charlson Comorbidity Index ([Formula: see text]). Multivariate analysis revealed that lower functional status (Modified Barthel Index per 10-point decrease: [Formula: see text], 95% CI: 7.37-11.82, [Formula: see text]) and advanced age ([Formula: see text], [Formula: see text]) were strong predictors for the "Rapidly Worsening Frailty" trajectory, while psychological factors including anxiety ([Formula: see text], [Formula: see text]) and depression ([Formula: see text], [Formula: see text]) were significant predictors for the "Slowly Progressive Frailty" trajectory. Frailty progression following acute myocardial infarction is heterogeneous, and distinct trajectory patterns can be identified using structural entropy clustering. These findings may support the development of differentiated nursing strategies for early identification of high-risk individuals, pending validation in multicenter settings.
Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are significant public health issues, particularly in sub-Saharan Africa, and are associated with genital inflammation and increased HIV acquisition risk. A substantial proportion of these infections are asymptomatic, limiting the effectiveness of syndromic management. The Genital InFlammation Test (GIFT), a novel rapid point-of-care (POC) test, was developed to detect elevated inflammatory biomarkers associated with genital inflammation. The first-in-field prototype of the GIFT device was evaluated in a multicenter observational study conducted in South Africa, Zimbabwe, and Madagascar. This study updates prior cost estimates using a hypothetical GIFT prototype in South Africa and extends the analysis to routine family planning services in Madagascar, and Zimbabwe. A provider-perspective, combining a top-down and bottom-up costing approach, was conducted at device evaluation observational study sites in Madagascar, South Africa, and Zimbabwe (n = 1 per country). Economic costs, including capital and recurrent expenditures, were collected through facility records, interviews, and self-reported provider timesheets to determine the incremental cost of integrating GIFT screening into family planning consultations. Research-related costs were excluded. A probabilistic sensitivity analysis using Monte Carlo simulation was performed to address parameter uncertainty, particularly around GIFT's estimated market price of US$5.00. The incremental cost per woman screened with GIFT was estimated to be US $6.46 (95% CI: US $1.98 - US $12.22) in Madagascar, US $9.05 (95% CI: US $3.78 - US $15.83) in South Africa, and US $8.28 (95% CI: US $3.04 - US $16.52) in Zimbabwe, slightly higher than previous estimates for South Africa (US $3.53 - US$ 5.32). Recurrent costs (personnel, supplies, and overheads) constituted more than 98% of this cost, with the GIFT device being the primary cost driver. Updated costs suggest slightly higher implementation costs than previous estimates. This analysis suggests that the affordability and potential scale-up of GIFT and other novel POC screening tools will depend heavily on their final market price. These findings provide essential economic evidence to inform further analyses on cost-effectiveness, affordability, and optimal integration of GIFT into routine sexual and reproductive healthcare services in low- and middle-income countries.
Champions are individuals who demonstrate strong commitment to promoting sustained implementation efforts through their expertise, enthusiasm, and influence, and are known to enable the implementation of evidence-based educational programs. However, existing research has predominantly examined champion effectiveness during implementation and early sustainment phases, with limited attention to their role in long-term program or innovation sustainment. This study investigated how champions influence organisational capacity for sustained program implementation over extended timeframes. A multiple case study design examined champion dynamics across three Australian organisations sustaining implementation of the Abecedarian Approach Australia (3a) for 10 or more years. Semi-structured interviews were conducted with 25 participants, including senior leaders, program managers, educational leaders, and practitioners. Thematic analysis informed by critical realist epistemology identified mechanisms through which champions influenced long-term sustainability. Cross-case analysis suggested the presence of what we term a 'champion paradox': the factors that make champions effective in driving implementation may simultaneously create systemic vulnerabilities that can threaten long-term program sustainability. Across these cases, the paradox appeared to operate through three interconnected mechanisms: (1) knowledge concentration, where expertise accumulates in individuals rather than organisational systems; (2) dependency creation, where organisations become reliant on champions for quality assurance, problem-solving, and program continuity; and (3) system capacity prevention, where champion effectiveness conceals organisational need for systematic capacity building. These mechanisms were interpreted as forming a self-reinforcing cycle that may strengthen champion dependency while inhibiting organisational independent capacity. The champion paradox framework invites reconsideration of widespread assumptions that individual champions inherently strengthen organisational implementation capacity. Findings suggest potential value of a shift from champion-dependent to more system-dependent implementation models, with implications for champion selection and development, organisational design, sustainability assessment, and policy frameworks. Implementation strategies may be strengthened by positioning champions as transitional resources focused on building collective organisational capacity rather than as permanent drivers of program quality.
In this study, a series of mechanically tunable CMOT hydrogels was successfully developed, which enable colon‑targeted delivery and controlled degradation via dynamic Schiff‑base cross‑linking. Among them, the moderately stiff CMOT‑M hydrogel best mimics the native mechanical microenvironment of intestinal tissue, significantly alleviating DSS‑induced colitis symptoms, restoring the expression of tight‑junction proteins (ZO‑1, occludin), and suppressing excessive production of inflammatory cytokines (TNF‑α, IL‑6, IL‑1β). Mechanistic investigations revealed that the CMOT‑M hydrogel modulates the Hippo signaling pathway through integrin‑cytoskeletal tension transmission, thereby precisely tuning the phosphorylation status and nuclear translocation of YAP/TAZ: during the acute phase, it moderately activates YAP/TAZ to promote epithelial proliferation and migration; during the repair phase, it suppresses excessive YAP/TAZ activation, guiding stem‑cell differentiation and preventing fibrosis. After loading with the herbal formula QCXPY (CMOT@QCXPY), the hydrogel further synergistically inhibits the IL‑6/STAT3 pathway and reshapes the gut microbiota, establishing a multidimensional regulatory network integrating mechanical, immune, and microbial cues. This work demonstrates that material stiffness serves as a critical design parameter that can promote mucosal regeneration through YAP‑mediated mechanosensing, offering a novel mechano‑therapeutic strategy for ulcerative colitis.
Fidelity is defined as the extent to which an intervention is delivered as intended. Without a clear understanding of fidelity to an intervention, variability in implementation may be confounded with observed outcomes, making valid conclusions about the intervention's efficacy challenging. The MIRROR-TCM (Multisite Replication of a Randomized Controlled Trial - Transitional Care Model) implementation evaluation, discussed here, sought to examine the delivery of the transitional care model (TCM) intervention and factors that influenced fidelity to the implementation of the intervention protocol over time. The TCM includes 10 core components, which aim to support older adults transitioning from the hospital back to the community. The objective of this paper is to describe the operationalization of a fidelity measure for the TCM intervention. Fidelity was operationalized at the element, component, and overall intervention levels. The TCM fidelity score examines 38 elements, which are broken into 8 components. Rules to evaluate an element-level, binary (0/1) fidelity scores were established by the study team, which consisted of clinicians and statisticians, and updated through feedback from the advanced practice registered nurses delivering the intervention. Component-level fidelity was assessed as the proportion of total elements completed from each component. Finally, overall fidelity is calculated as the proportion of required elements completed multiplied by 38 or the total possible elements to complete. Proper evaluation of fidelity to the delivery of an intervention is key in evaluating its implementation. This paper provides new methods to calculate fidelity for a complex intervention, which required the incorporation of 38 elements and nuances that did not require all patients to receive all elements, requiring the creation of clear rules for the exclusion of elements for a participant. The fidelity measure was employed throughout implementation and used to give feedback to the study team and improve fidelity. This paper outlines a novel methodology for flexible fidelity scoring in multicomponent interventions, incorporating rule-based exemptions to accommodate variability in real-world implementation. Future work needs to include validation of the metric through evaluation of fidelity at the participant level to examine its association with clinical outcomes in the parent MIRROR-TCM study, overall and by site.
Tuberculosis (TB) remains a leading cause of childhood morbidity and mortality, yet evidence on treatment outcomes and associated determinants in Northern Ghana remains limited. This study examined the prevalence, trends, and determinants of unsuccessful treatment outcomes among children with TB at Tamale Teaching Hospital from 2016 to 2024. A retrospective review of secondary data was conducted among children (< 15 years) diagnosed with TB at Tamale Teaching Hospital from 2016 to 2024. Data were extracted from the National Tuberculosis Programme registers. Treatment outcomes were defined according to WHO guidelines. Modified Poisson regression with robust standard errors was used to examine predictors of unsuccessful treatment outcomes, while logistic regression was performed as a sensitivity analysis. Analyses were conducted using Stata version 16 IC (StataCorp LLC, College Station, TX, USA). Of 1,842 TB cases, 245 were children, of whom 233 had documented treatment outcomes and were included in the analysis. The median age was 5 years (IQR: 2-10), and 58.4% were males. Pulmonary TB accounted for 63.5% of cases, while 13.7% had TB/HIV coinfection. The treatment success rate was 75.5% (176/233), while 24.5% (57/233) experienced unsuccessful outcomes, including 11.2% deaths and 13.3% loss to follow-up, with no cases of treatment failure. In multivariable analysis, children aged < 1 year (aRR: 3.04; 95% CI: 1.13-8.23), those aged 5-9 years (aRR: 3.51; 95% CI: 1.63-7.57), and rural residents (aRR: 1.70; 95% CI: 1.08-2.66) had a significantly higher risk of unsuccessful treatment outcomes. Sensitivity analysis using logistic regression confirmed these findings, and no significant associations were observed with sex, HIV status, type of patient, or disease classification. Nearly one in four children experienced unsuccessful TB treatment outcomes, mainly due to death and loss to follow-up. Younger age and rural residence were key predictors of poor treatment outcomes. Strengthening early diagnosis, decentralised care, and targeted adherence support for vulnerable groups is essential to improve outcomes.
Progressive back pain in elderly individuals may be caused by spine infections, metastatic cancers, or hematologic malignancies. Spine infections, such as spondylodiscitis, often result from hematogenous spread by staphylococci, streptococci, or gram-negative bacilli, whereas Clostridium species is a rare cause of spondylodiscitis. Lymphoma involving the spine can mimic infectious spondylodiscitis and lead to irreversible neurological damage. We report an elderly Thai woman with clostridial spondylodiscitis and lymphoma coexisting at the thoracic spine, highlighting the importance of a broad differential diagnosis in such cases. A 79-year-old Thai woman with osteoporosis and a previous T10 compression fracture, treated with denosumab, presented with worsening back pain radiating to both legs for five months, along with fatigue, anorexia, and a 7 kg weight loss. She developed a fever and weakness before admission. Initial treatment with ceftriaxone and cefixime temporarily alleviated her symptoms, but paralysis and sensory loss later worsened. At Siriraj Hospital, examination revealed complete paraplegia, and MRI showed spondylodiscitis and epidural abscesses at T10-T11, causing spinal cord compression. CT-guided biopsy identified gram-positive bacilli, and partial 16S rRNA sequencing showed 97.23% identity with Clostridium tarantellae. IV metronidazole was started. Additionally, tissue pathology revealed diffuse large B-cell lymphoma involving the thoracic spine. Staging CT showed extensive lymphadenopathy, but her bone marrow was unaffected. After four weeks of metronidazole, her pain improved, but neurological deficits remained. R-CHOP chemotherapy was initiated while continuing metronidazole. Unfortunately, she developed severe Acinetobacter baumannii pneumonia, which led to septic shock and respiratory failure. She died 74 days after admission. This case highlights the rare coexistence of spinal infection and lymphoma-an uncommon and challenging diagnosis in elderly patients with progressive back pain. The coexistence of infectious spondylodiscitis and spinal lymphoma is rare, posing diagnostic and therapeutic challenges that demand multimodal evaluation and prompt treatment to prevent complications and improve outcomes.
In the context of urban slum settings in Africa, there is limited knowledge about how food preparers make decisions as to the types of meals they serve in their households. Understanding what goes into food preparers' daily choices and the complexity of providing nutritious food in resource-scarce environments are crucial to addressing the challenges of food insecurity and malnutrition. This study explored perspectives on what food is prepared in households, the factors influencing meal choices and how decisions are made about what to serve and when. This qualitative study was conducted among persons living in two urban slums in Ibadan, Nigeria, who were most responsible for food preparation in their households. Trained research assistants conducted 30 in-depth semi-structured interviews in the local languages. Data collected were transcribed verbatim, then translated into English. The data were coded with NVivo software (Version 12) and analysed using thematic analysis. Of the 30 food preparers interviewed, 28 were women. Data analysis identified three major themes: what is eaten and how it is prepared; gendered decision-making and normative beliefs; and adapting food preparation to an environment of food scarcity. The food preferences described by all participants were similar, with most expressing a desire to make calorie-dense meals. Traditional "swallows", carbohydrate-rich dough-like dishes made from starchy roots, tubers or grains, were regarded as central to most meals, although it was highlighted that children often wanted processed foods, such as white rice and noodles. Decision-making over what to prepare was gendered, with men's preferences being favoured in addition to those of children. Food preparation was time-consuming and complicated by a lack of refrigeration and limited storage. This study offers valuable insights into the resourcefulness and resilience of slum-dwelling women in planning and preparing diverse meals in the context of living in resource-limited environments and balancing traditional family hierarchies. The findings will contribute to the development of contextually relevant interventions to improve access to nutritious foods, enhance food security, and ultimately contribute to the nutritional well-being of urban slum dwellers.