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Response of mid-lactation primiparous Holstein cows to the supplementation of rumen-protected methionine during the summer

by Caio R. Monteiro, Victor Augusto de Oliveira, Rabeche Schmith, João Pedro A. Rezende, Tales L. Resende, João A. Negrão, Marina A. C. Danés

This study aimed to evaluate the effects of rumen-protected methionine (RPM) supplementation on productive and physiological responses of primiparous Holstein cows during summer. We hypothesized that RPM supplementation would maintain or improve milk yield and composition due to beneficial physiological, redox, and inflammatory responses in cows exposed to summer heat. The trial was conducted in a randomized block design during nine weeks in Brazil using 80 primiparous cows (182 ± 64 DIM; 42.9 ± 4.7 kg/d milk). Cows were blocked by milk yield and DIM and assigned to a control diet (CON; no added RPM) or the same diet supplemented with RPM (Mepron®, Evonik) at 0.75 g/kg diet dry matter, targeting 20 g/cow/day (product contains 62% metabolizable methionine) to the average cow. Milk yield and composition, vaginal temperature, respiratory rate, and plasma samples were collected in weeks 3, 6, and 9. Data were analyzed using mixed models including treatment, week, and their interaction as fixed effects, and block and cow as random effects. Cows were maintained under naturally occurring summer conditions. Environmental monitoring during weeks 3, 6, and 9 indicated elevated temperature–humidity index (THI) values, with values remaining above the heat-stress threshold (THI > 68) for 68.3% of the monitored hours (mean THI = 70.6; range 61.0–84.4). Overall (least squares mean across weeks 3, 6, and 9), RPM increased milk yield by 2.0 kg/d (44.9 vs. 42.9 kg/d), protein yield by 50 g/d (1,464 vs. 1,414 g/d), lactose yield by 108 g/d (2,109 vs. 2,001 g/d), and total solids yield by 176 g/d (5,331 vs. 5,155 g/d). Lactose concentration was lower in RPM (4.71 vs. 4.76%). Fat yield was unaffected, but a treatment × week interaction was observed for fat content. Milk fatty acid (FA) profile was unchanged, although treatment × week interactions were observed for individual fatty acids (C16:0, C18:0, C18:1, and preformed FA). Plasma glucose was lower, and insulin was higher in RPM than in CON cows (39.3 vs. 43.2 mg/dL and 0.52 vs. 0.35 ng/mL, respectively). Antioxidant capacity improved, with RPM cows having greater ferric reducing antioxidant power (32.9 vs. 28.5 µM) and lower malondialdehyde (2.48 vs. 2.78 nmol/mL). Other biochemical, inflammatory, and immune markers were unaffected. Respiratory rate was slightly higher in RPM than in CON cows (55 vs. 50 breaths/min). Mean vaginal temperature did not differ between treatments; however, a treatment × time × hour interaction was observed. Supplementation with RPM improved milk and solids yield, and enhanced antioxidant capacity and insulin levels, supporting its use to improve metabolic resilience under warm conditions.

Evaluation of usability and acceptability of a Peruvian telemental health service for early assessment among vulnerable occupational workers: Mixed-method study with a user-centered design approach

by Jimmy Andreyvan Cainamarks-Alejandro, Liliana Cruz-Ausejo, Miguel Angel Burgos-Flores, Jaime Rosales-Rimache, Jonh Astete-Cornejo, David Villarreal-Zegarra

Background

The COVID-19 pandemic marked an increase in depressive, anxiety, and post-traumatic stress disorder symptoms, more specifically among healthcare workers, teachers, and police officers. These workers face external and occupational factors which had a significant impact on mental health, significant increase in workload and direct exposure to the virus, shortage of personnel protective equipment, and instances of abuse, including discrimination. Mental health care in primary care requires a process of early identification and timely referral of complex cases. Telehealth emerges as an effective alternative for addressing challenges in mental health care, although its implementation encounters obstacles.

Objective

To design a telehealth service that facilitates screening, initial management, and timely referral for mental health diagnoses in workers with prior SARS-CoV-2 infection, and to evaluate usability, acceptability, and user satisfaction.

Methods

Mixed-method study with a user-centered design approach involving key external and internal service users in three sequential stages (pre-design, co-design, and post-design). The study phases lasted 6 months, involving a total of 23 participants in the pre-design phase (contextual inquiry and preparation and training), 12 participants in the co-design phase (framing the issue, generative design, and sharing design), and in the post-design phase, 4 participants were involved in service implementation, and 81 participants—drawn from the subgroup of 134 users who received psychoeducation—were included in the efficacy assessment.

Results

The proposal included the development and evaluation of a service model guide and a telehealth software platform. First, the participants took part in a series of workshops (Pre-design, Co-design) where they provided ideas for meeting the product requirements, based on the Design Thinking methodology framework. The telehealth service model was named TelePsico CENSOPAS. It comprised four processes: a) Service promotion; b) User pre-identification; c) Appointment management; d) Psychoeducation counseling and referral. The Telehealth platform was designed through three cycles of an iterative process and integrated a proprietary development platform with third-party service technologies for communication support and information exchange. During post-design, the pilot test involved 698 screened patients; 193 were identified with mental health risks, and 134 of them received psychoeducation sessions. In addition to user acceptance, the usability score of the platform was 86.1 ± 16.9 SD, satisfaction dimensions of the service was 45.1 ± 7.2 SD for satisfaction with care processes, and 36.7 ± 5.2 SD satisfaction with psychological care.

Conclusion

The proposal for mental health telehealth services and its supporting platform was successfully developed and accepted by both internal and external users, particularly within well-structured occupational health services in workplaces serving vulnerable occupational groups. In addition, it achieved higher satisfaction and usability scores than Peru’s outpatient care services. These findings support the replicability of user-centered design frameworks—such as design thinking—within the occupational health sphere.

Views and Experiences of People With Dementia, Informal Caregivers and Professionals on Eating and Drinking Difficulties: A Qualitative Systematic Review

ABSTRACT

Aim

This study aims to explore the views and experiences of people with dementia, informal caregivers and professionals regarding eating and drinking difficulties.

Design

A qualitative systematic review was conducted.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used to conduct this systematic review. The quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, and the data were thematically synthesised using Thomas and Harden's three-stage method.

Data Sources

Six electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL and PsycINFO) were searched from their respective inception dates to August 2025 to identify relevant studies.

Results

Thematic analysis of the 16 included studies identified four key themes: (1) Physiological and psychological changes in people with dementia and caregivers; (2) factors influencing eating and drinking in people with dementia; (3) needs and recommendations for people with dementia, informal caregivers and professionals; (4) selection of eating methods for end-stage people with dementia.

Conclusions

Eating and drinking difficulties affect the well-being of both patients and caregivers. A good dining environment improves mealtime pleasure but demands caregivers' time and energy. All parties emphasised the importance of effective communication. In end-stage dementia, professional assistance is crucial for enteral nutrition decisions.

Implications for the Profession and/or Patient Care

Collaboration among patients, caregivers and professionals is vital for creating tailored nutritional plans and improving mealtime environments, thereby enhancing nutritional intake. In advanced dementia, providers must provide balanced information on comfort feeding versus enteral nutrition to aid decision-making.

Impact

What problems were addressed in this study? This study addressed the lack of a consolidated, tri-perspective understanding of eating and drinking difficulties in dementia care settings. What are the main findings? Four key themes were identified: physiological and psychological changes, influencing factors, stakeholder needs and end-of-life decision-making. Where and on whom will the research have an impact? This will impact care practices for people with dementia and inform the training and support of informal caregivers and healthcare professionals.

Network Analysis of Self‐Efficacy and Professional Resilience in Emergency Nurses: A Multi‐Center Cross‐Sectional Study

ABSTRACT

Objective

This study aimed to investigate the network structural characteristics of self-efficacy and professional resilience among emergency nurses, identify core nodes within the network, and elucidate the key interactive mechanisms between these constructs.

Design

Descriptive cross-sectional study.

Methods

A multi-center cross-sectional study was conducted from January to February 2025, involving 612 emergency nurses from 20 hospitals in Sichuan, China. Data were collected using a self-administered demographic questionnaire, the General Self-Efficacy Scale, and the Chinese Emergency Nurse Professional Resilience Tool. An adjacent network integrating professional resilience and self-efficacy was developed. Key covariates—including title, position, tenure in the hospital or emergency department, education, and exposure to workplace violence—were included as control variables. Network precision and stability were evaluated using the correlation stability coefficient and confidence intervals for edge weights. To further test the robustness of the network model, sensitivity analyses were performed by adding each significant covariate to the original model. The Network Comparison Test was then used to compare the covariate-adjusted and unadjusted networks, assessing differences in network structure, overall strength, and edge weights.

Results

The analysis identified S9 as the central node in the network. The overall network showed satisfactory stability and precision. The Network Comparison Test showed no significant differences in network structure or global strength between the adjusted and unadjusted models, indicating that the network was stable and robust to covariate adjustment.

Conclusion

This network analysis revealed the interaction mechanisms between self-efficacy and professional resilience among emergency nurses through contemporaneous network modelling and identified S9 as the core node, suggesting that this coping strategy plays a key role in regulating psychological resources. The overall network demonstrated good stability and precision, with no statistically significant differences between the adjusted and unadjusted models according to the Network Comparison Test. These findings indicate that the network structure was robust to covariate adjustment and provide a reference for developing and optimising intervention strategies to enhance professional resilience among emergency nurses.

Implications

For Emergency Nurses and the Management of Emergency Nursing Practice: What problem does this study address?

This study addresses the gap in understanding how self-efficacy and occupational resilience interact in emergency nurses under high-stress conditions.

Key Findings

A contemporaneous network analysis revealed a central node linking self-efficacy and resilience, highlighting key pathways in their mutual influence.

Impact

The findings offer practical guidance for emergency nursing management, supporting the development of targeted strategies to strengthen nurses' resilience, enhance professional competence, and improve the quality of emergency care.

Reporting Method

This study is reported using the STROBE guidelines.

Patient or Public Contribution

No Patient or Public Involvement: This study did not include patient or public involvement in its design, conduct, or reporting.

Healthcare Professionals' Descriptions of Contextual Factors Affecting Complex Aortic Surgical Care: A Secondary Analysis Using the Fundamentals of Care Framework

ABSTRACT

Aim

To explore how factors in the complex aortic surgical care context can affect care provision towards patients' postoperative recovery.

Design

Secondary qualitative analysis.

Methods

Results about patients' recovery after complex aortic surgery was presented in focus groups with healthcare professionals in 2022. Reflexive thematic analysis, using the Fundamentals of Care framework, was conducted to explore contextual factors affecting care provision.

Results

Healthcare professionals' descriptions resulted in one main theme: Care provision is challenged by discrepancies in values, goals and norms and unclear responsibilities within the context, and two subthemes: Values, goals and norms determine what care is provided; Taking responsibility for care requires resources, evaluation and feedback.

Conclusion

Healthcare professionals describe care provision as affected by a dynamic integration of contextual factors. Healthcare professionals need to be made aware of their own role in this context. Care provision needs to be guided by feedback from patients and healthcare professionals, and work with patients' resources at both an individual, system and societal level.

Implications for the Profession

The results provide knowledge regarding how contextual factors in dynamic integration can affect care provision in a complex surgical context. Healthcare professionals, leaders and policy makers all have responsibility to focus on patients' values and goals, and empower adequate care through feedback loops and resource management.

Impact

The context-of-care dimension of the Fundamentals of Care framework has been scarcely described. Our results illustrate how an integration of factors affects care provision, where values, goals, and norms affect what care is provided, and responsibility for care belongs to everyone in the care system. The results can contribute to the description of the context-of-care dimension within the framework and enable professionals to understand how they, as part of the context, could affect care towards patient recovery.

Reporting Method

This study adhered to the Equator research reporting checklist: Consolidated criteria for reporting qualitative research: a 32-item checklist for interviews and focus groups.

Patient or Public Contribution

No patient or public contribution.

Investigating the impact of residual refraction within {+/-}1.0 dioptre on uncorrected distance visual acuity in pseudophakic eyes: a cross-sectional study

Por: Li · D. · Zhang · J. · Jin · L. · Han · X. · Chen · L. · Liu · Y. · Cai · W. · Cao · Q.
Objectives

To investigate the impact of residual refraction within ±1.0 dioptre (D) on uncorrected distance visual acuity (UDVA) in pseudophakic eyes.

Design

Cross-sectional study.

Setting

This study was based on retrospectively collected electronic refraction records from a tertiary care academic ophthalmology centre in southern China between May 2022 and July 2025.

Participants

Patients aged ≥40 years who underwent uneventful phacoemulsification cataract surgery with in-the-bag monofocal intraocular lens implantation and achieved a postoperative corrected distance visual acuity (CDVA) of ≤0.1 logarithm of the minimum angle of resolution were enrolled. They were stratified by astigmatism subtypes: minimal astigmatism (

Outcomes measures

Postoperative evaluation (≥1 month) included spherical equivalent (SE) refraction, UDVA and CDVA. UDVA was compared across eyes with SE intervals of 0.50 D within ±1.0 D. ORs were calculated to assess the relative risk of failing to achieve a UDVA of 0.1 or better for postoperative SE within ±1.0 D, using 0.00 D as the reference.

Results

The study included 1333 eyes from 1333 patients (mean (SD) age, 66.1 (8.96) years; 532 male (39.9%)). Overall, and particularly in the minimal astigmatism (

Conclusions

The impact of refractive errors (≤1.0 D) on UDVA was associated with the magnitude and type of astigmatism. Residual astigmatism of ≥0.50 D exerted a significant negative effect on UDVA. A plano SE (0 D) was optimal for minimum and WTR astigmatism, whereas slight hyperopia yielded superior UDVA in ATR and oblique astigmatism.

Culturally appropriate sexual health interventions for STBBI and HIV among racialised immigrant communities in Western nations: a scoping review protocol

Por: Kwame · A. · Maina · G. · Langman · E. · Ndubuka · N. · Caine · V. · Spence · C. · Maposa · S. · Kamrul · R. · Mason · N. · Etowa · J. · Eaton · A. D. · Caron-Roy · S. · Abdulrasheed · A. · Guliak · D. · Chowdhury · I. · Ahmed · A. · Nyoni · N. · Hanson · J. · Alvarez · A.
Introduction

Racialised immigrant communities in Western nations face disproportionate risks for sexually transmitted and blood-borne infections (STBBIs) due to systemic barriers, including racism, stigma and limited access to culturally appropriate care. While the need is well-established, a comprehensive synthesis of effective, culturally responsive sexual health interventions is lacking. This scoping review aims to map the available evidence on sexual health intervention needs and protective factors of racialised immigrants, and to identify and describe existing culturally appropriate programmes in Western nations.

Methods and analysis

The review will follow the JBI methodology for scoping reviews and be reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search strategy, developed and peer-reviewed by a health sciences librarian, will be executed in MEDLINE, Embase, CINAHL and Scopus, alongside grey literature sources, with no date limit. Two independent reviewers will screen titles/abstracts and full texts against the inclusion criteria. Data will be extracted using a standardised tool, analysed via narrative synthesis and framed by a socio-ecological model to categorise interventions across individual, interpersonal, community and structural levels.

Ethics and dissemination

Ethical approval is not required for this review. Findings will be disseminated through a peer-reviewed publication, academic presentations and tailored summaries for community organisations and policy-makers to ensure practical application.

Review registration

Open Science Framework (https://osf.io/9qah6).

Safety and efficacy of connecting the residual ear to the cartilage scaffold in the first-stage versus second-stage surgery: a protocol of a randomised controlled trial in non-expanded auricular reconstruction for concha-type microtia

Por: Zhang · X. · Chen · Z. · Chen · M. · Wang · Y. · Du · L. · Cai · Z. · Jiang · Z.
Introduction

Concha-type microtia, classified as a milder form of microtia under Nagata’s classification, is characterised by the presence of more normal ear subunits compared with other types. The non-expanded auricular reconstruction using autologous rib cartilage is a standard procedure treating conchal microtia, and this operation typically comprises two stages. To maximise the utilisation of native auricular cartilage, the lower half of a patient’s ear is preserved as residual ear, which should be connected to the rib cartilage scaffold in this operation. However, it remains unclear whether this connection should be performed in the first-stage or second-stage surgery. Current literature lacks sufficient evidence to determine the safer and more effective approach. Thus, we plan to conduct this randomised controlled trial to formally compare the safety and efficacy of first-stage versus second-stage connection, hypothesising that second-stage connection may be a better choice since it may reduce skin cutting, operative risk and improve recovery.

Methods and analysis

This is a single-centre, randomised controlled trial comparing two surgical treatments. Based on sample size calculations, a total of 78 eligible patients will be randomised with a 1:1 allocation. The control group will be treated with connecting the residual ear with the framework in stage 1, while the experimental group will be treated with connecting the residual ear with the framework in stage 2.

The safety of the surgery will be evaluated based on the grade-A healing rate and the incidence of complications (infection, haematoma, flap or skin necrosis and cartilage scaffold exposure). Efficacy of the surgery will be assessed using the Patient and Observer Scar Assessment Scale (POSAS) and Glasgow Benefit Inventory (GBI) scores. Patients will be scheduled for follow-up 3–6 months after each surgery. Descriptive analyses will be performed to summarise baseline demographics. The incidence of grade-A healing and complications will be analysed using the 2 test. GBI and POSAS scores of the two groups will be analysed using independent-samples t test. A p value

Ethics and dissemination

This study was approved by the Ethics Committee of Sichuan Provincial People’s Hospital (no. 2025-256-1) on 9 April 2025, and conformed to the Declaration of Helsinki. At the time of manuscript submission, patient recruitment began in April 2025 and is expected to continue until January 2027. Surgical procedures and follow-up will continue until February 2028. Trial results will be published in peer-reviewed journals and will be disseminated to the media and the public.

Trial registration number

NCT06763991.

Exploring Core and Bridge Symptoms Among People With Type 2 Diabetes Mellitus in China: A Network Analysis

ABSTRACT

Aim

To explore the network characteristics of symptom clusters in people with type 2 diabetes mellitus through network analysis, identify the core and bridging symptoms within the symptom network, and provide a foundation for targeted interventions and symptom management in people with T2DM.

Design

A cross-sectional survey.

Methods

A total of 360 people with T2DM who were hospitalised in the endocrinology departments of two hospitals with Grade A in Daqing City between August 2024 and February 2025 were selected using a convenience sampling method. The symptoms of people with T2DM were measured using the Chinese version of the Diabetes Symptom Checklist-Revised (DSC-R). Symptom clusters were identified through factor analysis, and network analysis was used to identify core and bridging symptoms. This research adhered to the STROBE guidelines.

Results

Six symptom clusters were obtained from factor analysis, which were psychological-behavioural symptom cluster, ophthalmological-neuropathy symptom cluster, cardiovascular symptom cluster, metabolic symptom cluster, body symptom cluster and nephrotic symptom cluster. Symptom network analysis revealed that ‘Deteriorating vision’ exhibited the highest strength centrality and expected influence. The top three symptoms with the highest bridge strength and bridge expected influence were ‘Aching calves when walking’, ‘Queer feeling in the legs or feet’ and ‘Sleepiness or drowsiness’.

Conclusions

People with T2DM commonly exhibit a range of symptoms. ‘Deteriorating vision’ is the most core symptom in people with T2DM. ‘Aching calves when walking’, ‘Queer feeling in the legs or feet’ and ‘Sleepiness or drowsiness’ are identified as the bridging symptoms in the network analysis. Healthcare professionals can design targeted interventions based on symptom clusters, core symptoms and bridging symptoms, thereby improving the efficiency of symptom management and optimising outcomes for people with T2DM.

Patient or Public Contribution

No patient or public contribution.

Patient Engagement Interventions to Improve Medication Management of Older Patients Across Transitions of Care: A Mixed Methods Systematic Review

ABSTRACT

Aims

Identify and describe patient engagement interventions used to improve medication management in older adults during transitions of care.

Design

A mixed-methods systematic review.

Methods

A comprehensive search of all study designs was conducted. Studies were categorised using the ladder of patient and family engagement, a framework that positions engagement from low (passive) to high (active partnership) patient engagement.

Data Sources

Six databases were searched from inception to April 2024.

Results

The search yielded 29 reports, with 25 classified as studies. Most interventions (n = 19, 76%) were low-level interventions that comprised informing patients in a passive manner. Interventions that facilitated high-level engagement (n = 6, 24%) where patients were integrated in the decision-making process were associated with consistently improved patient and healthcare long-term outcomes.

Conclusions

While low and high-level engagement interventions were associated with significantly decreased hospital readmission rates, high-level interventions consistently demonstrated positive patient outcomes. Interventions supporting older adults beyond discharge achieved meaningful and lasting patient and healthcare outcomes for older adults.

Implications for the Profession and/or Patient Care

Findings provide clinical reference for designing engagement interventions, highlighting long-term benefits of partnership-based approaches and continuity beyond discharge.

Impact

Engagement in medication management during transitions of care varied significantly. High-level engagement was consistently linked to improved patient and healthcare outcomes but was often resource intensive. This review identifies the need to design balanced interventions that align with the preferences of older adults and real-world contextual healthcare settings.

Reporting Method

PRISMA guidelines.

Patient or Public Contribution

No patient or public contribution.

Protocol Registration

PROSPERO (registration number CRD42024557385).

Effects of Nursing Workforce and Work Environment on Health System Resilience in Public Health Emergencies: A Multicenter Cross‐Sectional Study

ABSTRACT

Aim

The study examines the associations between nursing competence, work environment, and health system resilience. It also analyzes how nursing competence and work environment relate to different patterns of health system resilience.

Design

A multiple center cross-sectional study was conducted between December 2023 and January 2024 across 33 hospitals in eastern China, involving 2435 nurses.

Methods

Questionnaires measuring nursing competence, work environment resources, nurse disaster resilience, and organizational commitment to resilience were utilised, along with the collection of additional personal demographic data. Structural equation modelling and cluster analysis were performed to explore the underlying mechanisms within the overall model and across multiple groups. Multivariable regression was conducted to identify variables associated with resilience in different subgroups.

Results

Structural equation modelling demonstrated significant influences of nursing competence and work environment support on system resilience. Cluster analysis identified four resilience patterns: strong, marginal, low, and critical vulnerability. Strong resilience correlated with balanced individual-organizational resources, while vulnerable systems relied heavily on environmental support.

Conclusion

Our findings support policymakers and managers in developing systematic strategies with distinct focal points—targeting nurse workforce investment and optimised work environment—to enhance health system resilience across varying levels of public health emergencies.

Implications for the Profession

This study validated the framework connecting individual and organizational resilience, offering evidence-based insights for nurse training and resource allocation to enhance healthcare systems' adaptability during disasters.

Impact

The study addressed how nursing competence and work environment significantly influenced resilience during public health emergencies, identified four resilience patterns, and provided insights to guide policymakers and healthcare managers in developing targeted, effective strategies.

Reporting Method

Strengthening the Reporting of Observational studies in Epidemiology checklist.

Patient or Public Contribution

No patient or public contribution.

Inhibition of TREM1 attenuates myocardial ischemia-reperfusion injury-induced cardiomyocyte pyroptosis by suppressing the activation of the NF-κB signaling pathway

by Xiaohui Xu, Liang Cai, Xuan Dang, Jianbin Han, Yan Kou, Chunyan Rong, Junjie Kou

Background

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of inflammatory responses and plays a critical role in the pathogenesis of various infectious diseases. Notably, emerging evidence suggests that TREM-1 is also involved in the development and progression of cardiovascular diseases, such as atherosclerosis and atrial fibrillation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unclear. This study aimed to investigate the role of TREM-1 in myocardial I/R injury and to explore the potential underlying molecular mechanisms.

Methods

A hypoxia/reoxygenation (H/R) model was established using HL-1 cardiomyocytes subjected to 6 hours of hypoxia followed by 6 hours of reoxygenation. Pyroptosis levels were assessed by Hoechst-PI staining, lactate dehydrogenase (LDH) release assay, CCK-8 assay, and Western blot analysis. In vivo, a myocardial I/R injury model was established in C57BL/6 mice by subjecting them to 30 minutes of ischemia followed by 24 hours or 7 days of reperfusion. Evaluation was performed using TTC staining, Western blotting, echocardiography, histochemical staining, and immunohistochemistry.

Results

In this study, we found that TREM-1 expression was significantly upregulated in both in vitro and in vivo models of myocardial ischemia-reperfusion injury (MIRI). Pharmacological inhibition of TREM-1 by LR12 effectively reduced the levels of cardiomyocyte pyroptosis and suppressed activation of the NF-κB signaling pathway. In addition, LR12 treatment alleviated myocardial inflammation and fibrosis and improved left ventricular function in mice.Intervention experiments with MCC950, a specific NLRP3 inhibitor, confirmed that NLRP3 inhibition could mimic the anti-pyroptotic effect of LR12 and reduce the expression of pyroptosis-related proteins. Immunofluorescence experiments further verified that inhibition of NF-κB decreased NLRP3 expression, clarifying the association between TREM-1 downstream signals and NLRP3. Long-term follow-up experiments showed that LR12 treatment significantly reduced the area of myocardial fibrosis at 7 days after reperfusion.

Conclusion

Our findings indicate that inhibition of TREM-1 alleviates cardiomyocyte pyroptosis during MIRI by suppressing activation of the NF-κB signaling pathway. Therefore, TREM-1 may represent a promising therapeutic target for the treatment of myocardial ischemia-reperfusion injury.

Impact of patient empowerment on continuity of care needs in patients with stable COPD: the mediating role of eHealth literacy in a cross-sectional study from China

Por: Chen · C. · Feng · J. · Cai · B. · Qian · Y.
Objective

To explore the relationships among continuity of care needs, patient empowerment and eHealth literacy in patients with stable chronic obstructive pulmonary disease (COPD), and to further identify the potential mediating role of eHealth literacy.

Design

Cross-sectional study.

Setting

A tertiary care hospital (Level 3A, the highest level in the Chinese hospital classification system) in Shanghai, China.

Participants

The study participants consisted of 219 patients with stable COPD who visited or underwent follow-up at the outpatient clinic between December 2023 and May 2024.

Outcome measures

The Continuity of Care Needs Questionnaire, COPD Patient Empowerment Evaluation Scale and eHealth Literacy Scale (eHEALS) were used to assess 219 patients with stable COPD. Univariate analysis, Pearson correlation analysis and mediation analysis were performed.

Results

The mean Continuity of Care Needs score was 24.17 (SD=2.74), with medication guidance needs being the highest-scoring domain. The COPD Patient Empowerment score was 84.37 (SD=11.58), and the eHEALS score was 23.37 (SD=6.06). Pearson correlation analysis showed that continuity of care needs were negatively correlated with patient empowerment (r=–0.930, 95% CI –0.946 to –0.910) and eHealth literacy (r=–0.976, 95% CI –0.982 to –0.969), while patient empowerment was positively correlated with eHealth literacy (r=0.919, 95% CI 0.895 to 0.937) (all p

Conclusions

Patients with stable COPD demonstrated high continuity of care needs, with eHealth literacy partially mediating the relationship between patient empowerment and continuity of care needs. Healthcare providers should consider patients’ eHealth literacy to enhance patient empowerment and develop personalised continuity of care strategies.

Temperature-dependence of early development of zebrafish and the consequences for laboratory use and animal welfare

by Angelina Miller, Katja Lisa Schröder, Karsten Eike Braun, Caitlin Steindorf, Richard Ottermanns, Martina Roß-Nickoll, Henner Hollert, Thomas Backhaus

Zebrafish (Danio rerio) are widely used in biological research, but the impact of incubation temperatures on developmental endpoints is still insufficiently studied. This study quantifies developmental differences in zebrafish embryos incubated at 26°C and 28°C, focusing on key endpoints (heartbeat onset, hatching time, eye size, yolk sac consumption, and body length). For this purpose, we recorded a high-resolution time series comprising hourly observations of early developmental stages and key events and bi-hourly observations of body length until 120 hours post fertilization. Additionally, we recorded a low-resolution time series at 72, 96, and 119 hours post fertilization for detailed measurements of eye size, yolk sac area, and body length. Embryos incubated at 26°C showed consistent delays in developmental stages compared to those at 28°C, with delays becoming more pronounced at later stages. Yolk sac consumption was delayed by about 19.8 hours at 26°C by 119 hours post fertilization, suggesting a delayed onset of independent feeding. These findings suggest that time-based regulatory limits for rearing zebrafish, such as the 120-hour threshold in German regulations (TierSchVerV), do not fully account for temperature-dependent development. The results emphasize the need for guidelines linking incubation temperatures to developmental progress.

Rationale and design of the AlloFIST trial: a phase I/IIa study to evaluate dose escalation of allogeneic adipose-derived stroma/stem cells for the treatment of Crohns fistula

Por: Buscail · E. · Gilletta de Saint Joseph · C. · Lebrin · M. · Frument · I. · Gross · F. · Bournet · B. · Buscail · L. · Culetto · A. · Mokrane · F. · Delchier · M. C. · Quelven · I. · Daguzan · C. · Pugnet · G. · Duffas · J. P. · Ghouti · L. · Philis · A. · Carrere · N. · Lepage · B. · Le C
Introduction

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract distinguished by progressive bowel damage with a risk of structuring and penetrating complications. It is characterised by focal or segmental transmural inflammation that disrupts intestinal mucosal integrity and favours the development of abscesses and fistulas. Perianal fistula develops in 13%–39% of patients with CD. Their care is difficult but improves with medical and surgical treatment to preserve anal continence and avoid a maximum proctectomy. Combined treatment with seton placement and concomitant anti-TNF (infliximab, adalimumab) allows wound healing in 40%–70% of cases. The currently available treatments are not curative and fail to provide a long-term resolution. The injection of adipose stromal cells is currently being evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischaemia, osteoarthritis, systemic sclerosis, etc). Immunoregulatory and anti-inflammatory properties of AdMSC (adipose-derived stroma/stem cells) are responsible for accelerating healing and represent an innovative approach for treating perianal fistulas associated with CD.

Methods and analysis

This phase I/IIa study is designed to assess the treatment of complex perianal fistulas linked with CD after failure of conventional treatment by injection of AdMSC (CellReady) into the fistula. Two doses of associated AdMSC will be tested for a dose escalation (5x107 and 10x107 cells) and injected into the wall of the fistula. Those eligible for inclusion include patients with controlled luminal CD characterised by a Harvey-Bradshaw score below or equal to eight and diagnosed on clinical, endoscopic, histological and/or radiological criteria, a colonoscopy dating back less than 1 year without ulcer in the rectum and presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports. All patients must have social security insurance or equivalent social protection. The aim of this study is to determine the optimal dose corresponding to maximum efficacy 6 months after injection of cells with a treatment-related adverse event rate of 20%.

Ethics and dissemination

The EU CT number 2024-511821-75-00 was approved by the following Ethics Committee: CPP (committee for the protection of persons in French: comité de protection des personnes) Ouest 1 – Tours #2024UEMED-18 and ANSM (French Agency for the Safety of Health and Medicinal Products in French : Agence nationale de sécurité du médicament et des produits de santé) #2024-511821-75-00 (Sponsor number RC31/13/7030, protocol V2.1). The results will be disseminated through conventional scientific channels.

Trial registration number

NCT06636032.

The results will be disseminated through conventional scientific channels.

Effects on recurrence and quAlity-of-life of iliac vein Stenting angioplasTy for patients with Varicose veins combined with severE Iliac veiN compression: a protocol for a prospective, multicentre, randomised clinical trial (EAST-VEIN trial)

Por: Cong · L. · Cai · F. · Chang · Y. · Hua · Z. · Hu · Z. · Hao · H. · Ma · J. · Ma · L. · Wang · L. · Wang · L. · Xia · Y. · Yuan · H. · Yu · W. · Zhang · F. · Zhuang · H. · Zhang · R. · Zhang · Z. · Yang · T. · Yang · L.
Introduction

Both varicose veins (VV) and iliac vein compression syndrome (IVCS) can cause skin damage and functional impairment in the lower extremities, and these issues often coexist. However, the question of whether IVCS exacerbates VV progression and leads to differences in the surgical outcomes of therapy for VV remains unanswered. Therefore, no high-level evidence-based medical data is available to support the concomitant use of iliac vein stenting in patients with VV and severe IVCS, and treatment protocols vary significantly among different centres. This study will investigate the effects of concomitant iliac vein stenting on post-procedure varices recurrence and quality of life (QoL) on the basis of a prospective, multicentre, randomised controlled trial with the goal of providing a foundation for the standardised treatment of patients with VV and IVCS.

Methods and analysis

This prospective, multicentre, randomised controlled trial will enrol 160 patients with VV and severe IVCS. All patients will be randomly divided into either the VV endovenous thermal ablation (ETA) alone group or the VV ETA combined with iliac vein stenting (ETAS) group. Baseline data will be collected and follow-up will be conducted at 1, 6, 12 and 36 months after the procedure. The primary outcome is post-procedure VV recurrence (as assessed by clinical and ultrasound examination). Secondary outcomes include QoL scores (according to the Aberdeen Varicose Vein Questionnaire, the Chronic Lower Limb Venous Insufficiency Questionnaire, the European Quality of Life Five-Dimensions, and the Venous Clinical Severity Score) and the incidence of post-procedure complications. Bleeding complications resulting from anticoagulation therapy and stent-related complications (such as restenosis and deep vein thrombosis) will also be recorded for patients in the ETAS group.

Ethics and dissemination

This study has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (approval number: XJTU1AF2024LSYY-075). Written informed consent has been obtained from all participants. The final results of this study will be published in a peer-reviewed journal and presented at national or international conferences.

Trial registration number

This protocol was registered on chictr.org.cn prior to enrolment, which began on 19 June 2024 (Registration ID: ChiCTR2400085815).

Effects of different folic acid supplementation doses on subsequent pregnancy outcomes in women with a history of pregnancy loss: study protocol for a multicentre randomised controlled trial

Por: Liu · C. · Cai · Z. · Du · L. · Fang · Z. · Yang · H. · Wu · H. · Li · Q. · Yan · A. · Chen · L. · An · R. · He · Q. · Zhang · X. · Ren · Y. · Wang · F.
Introduction

Folic acid is crucial for fetal development, particularly during early pregnancy. Studies suggest that high folic acid intake (≥800 µg/day) may be associated with a reduced risk of miscarriage. However, the impact of an 800 µg dose on pregnancy outcomes in women with prior pregnancy loss currently remains unclear.

Methods and analysis

We will conduct a multi-centre randomised controlled study comparing 800 µg and 400 µg in women with previous pregnancy loss. The primary outcome is live birth. Secondary outcomes include early pregnancy loss, ongoing pregnancy at 24 gestation weeks, homocysteine (Hcy) reduction, maternal and perinatal outcomes. We plan to recruit 1116 women (558 women per group). Data analysis will follow the intention-to-treat principle and per-protocol. Subgroup analysis will be conducted based on Hcy levels, previous pregnancy losses and body mass index.

Trial registration number

ChiCTR2500100255.

Checklist of Paediatric Advance Care Planning: A Delphi Study

ABSTRACT

Aim

To develop a comprehensive decision-making checklist for paediatric advance care planning tailored to the needs of terminally ill children and their families.

Design

A Delphi Study.

Methods

Underpinned by Delphi methodology, a four-phase procedure was adopted: (1) drafting items by the working group, (2) refining items based on an experts' survey, (3) further refining based on the same experts, and (4) final adaptations and approval. This study was initiated by the Paediatric Palliative Care Subspecialty Group of the Paediatrics Society of the Chinese Medical Association. The process involved 60 healthcare providers (physicians, nurses, and social workers) from 14 paediatric palliative care teams.

Results

The developed checklist included 5 topics, 24 subtopics, and 45 items. Five topics were (1) medical and nursing decision-making, (2) social support planning, (3) psychological support planning, (4) spiritual support planning, and (5) posthumous affairs planning. This checklist addresses symptom management for terminally ill children, integrating support for their psychological, social, and spiritual well-being, and addresses the care needs of their family members.

Conclusions

The study provided a paediatric advance care planning checklist derived from the expert consensus that includes key elements and items.

Implications

This checklist provides healthcare providers with a structured framework to set paediatric advance care planning and ensure that all aspects of children's well-being and their families' needs are considered. This study also lays an evidence-based foundation for the design of related documents.

Impact

This study developed a comprehensive paediatric advance care planning checklist with 5 topics, 24 subtopics, and 45 items. This study provides a comprehensive decision-making checklist for healthcare providers and families, ensuring that critical decisions are addressed timely.

Reporting Method

This article is presented in accordance with the CREDES guidelines.

Patient or Public Contribution

Limited patient and public involvement was incorporated, focusing on reviewing the initial checklist draft.

Intelligent voice-interactive tailored communication system (ScreenTalk) to improve colorectal cancer screening uptake among first-degree relatives of colorectal cancer patients: study protocol for a cluster-randomised type I hybrid effectiveness-implemen

Por: Lin · S. · Luo · B. · Cai · L. · Qiu · L. · Li · H. · Liu · W. · Luo · Y. · Yuan · Y. · Peng · Z. · Bai · Y.
Introduction

First-degree relatives of colorectal cancer (CRC) patients have a twofold to fourfold increased risk of CRC. Tailored communication interventions have shown efficacy in improving their risk awareness and screening participation. While computer-based tailoring systems offer convenience, they often overlook the integration of healthcare professionals’ verbal input, potentially limiting effectiveness and long-term impact. To address this gap, we developed ScreenTalk, an intelligent voice-interactive tailored communication system that employs intelligent speech interaction to automate the tailoring process, enhance message credibility and improve scalability within CRC screening workflows.

Methods and analysis

This study is a two-arm, cluster-randomised controlled trial with a hybrid type I design involving 314 participants across three tertiary general hospitals in Guangzhou, China. Participants in both groups will receive usual care. Additionally, the intervention group will receive a 1-month tailored intelligent voice-interactive intervention, whereas the control group will receive unrelated health education to control for attention. Screening uptake (primary outcomes) and health beliefs (secondary outcomes) are measured at baseline and at 3 months, 6 months, 9 months and 12 month post the intervention. Implementation outcomes including reach, implementation, adoption and maintenance will be assessed through questionnaire, qualitative interviews and tailored system record.

Ethics and dissemination

The trial has been approved by the Ethics Committee of the Sun Yat-sen University (IRB No. L2024SYSU-HL-054). Information on the purpose and process of this study will be provided to the participants before recruitment, and written signatures will be collected from all participants to ensure their voluntary participation and protection of their rights and privacy.

Trial registration

NCT06710860 on ClinicalTrials.gov. Registered 26 November 2024. Date and version: 3.0, 14 July 2025.

Using participatory methods to develop a narrative intervention to alleviate distress in children hospitalised with TB in South Africa: The DIMPle project

by Caitlin D. October, Dzunisani P. Baloyi, Lario Viljoen, Rene Raad, Dillon T. Wademan, Megan Palmer, Juli Switala, Michaile G. Anthony, Karen Du Preez, Petra De Koker, Anneke C. Hesseling, Bronwyne Coetzee, Graeme Hoddinott

Children who are hospitalised for tuberculosis (TB) experience challenges that put them at risk of developing emotional, behavioural, and social difficulties. In this methodological paper, we showcase the development of a narrative intervention toolkit with key components of the resulting version 1.0 tool. The study design was participatory and pragmatic, with researchers working with the routine staff of TB hospital wards, children admitted and their caregivers, to iteratively understand and improve children’s experiences of hospitalisation. The project included three phases: (1) a situational analysis to map children and healthcare providers’ perspectives on priorities and potential intervention components, (2) co-development of a beta-version of the intervention, and (3) piloting and incremental refinement toward a version 1.0 of the intervention. The intervention toolkit combined a series of activities alongside the story of ‘Courageous Curly’ to facilitate children’s engagement with their own experiences of hospitalisation, including psychosocial and treatment challenges, captured, and described throughout data collection. We found that dividing the story into short chapters facilitated children’s engagement with the section of story that is being told on a specific day. Each chapter of the story follows/mimics a different stage children can expect during their treatment journey while hospitalised for TB care. Implementation and evaluation of such interventions can mitigate the psychosocial impact of TB in children and inform policies to improve their overall TB care.
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