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<i>IRX3</i> depletion promotes early cardiac commitment of hiPSC-Derived Cardiomyocytes

by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger

Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing IRX3 expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting IRX3 enhances hiPSC-CM differentiation. IRX3-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, IRX3-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that IRX3 expression peaks during the early stages of cardiomyocyte differentiation, whereas IRX3-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and TBX5, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.

Add-on tocilizumab versus placebo for resistant major depression in psychiatric outpatients with low-grade inflammation in a tertiary public hospital in Southern Brazil: randomised triple-blind clinical trial protocol

Por: Portal · P. H. G. · Peixoto · G. N. · de Matos · M. R. · da Silva · L. C. N. · Alexandrino · G. B. · Dutra · P. H. G. · Carniel · B. P. · da Rocha · N. S.
Introduction

Emerging evidence supports a role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in the pathogenesis of treatment-resistant major depressive disorder (TRD). However, interventional studies targeting IL-6 in this population remain scarce. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 signalling and is approved for the treatment of autoimmune conditions such as rheumatoid arthritis. The primary objective of this study is to examine whether IL-6 inhibition via tocilizumab can impact depressive symptoms, inflammation-related biomarkers and cognition in patients with TRD. A secondary objective is to compare the biological profiles of patients with TRD with elevated inflammation to those of healthy controls.

Methods and analysis

This is a proof-of-concept, randomised, parallel-group, triple-blind, placebo-controlled clinical trial. 22 adult outpatients diagnosed with TRD and evidence of low-grade inflammation (serum C reactive protein≥3 mg/L) will be randomised (1:1) to receive either one intravenous infusion of tocilizumab (8 mg/kg; maximum 800 mg) or normal saline, administered as an add-on to their ongoing treatment. Psychiatric, cognitive and biomarker assessments will be performed at baseline and at follow-up visits on days 7, 14 and 28 post-infusion. Additionally, 10 healthy controls with no psychiatric history will undergo the same baseline assessments for biomarker comparison.

Ethics and dissemination

The study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (Project number: 2025-0245, CAAE: 88904825.7.0000.5327). Findings will be disseminated through peer-reviewed publications, scientific meetings and, on request, lay summaries for participants.

Trial registration number

NCT07052058.

Effect of a culturally adapted heart-healthy diet with phytosterols and/or krill oil on lipid-related outcomes in familial hypercholesterolaemia: protocol for a multicentre randomised controlled trial in Brazil

Introduction

An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.

Methods and analysis

The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.

Ethics and dissemination

This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.

Trial registration number

NCT06331195.

How do acute worsening events influence daily life and healthcare-seeking behaviour in patients with COPD: an international multicountry qualitative study

Por: Dijk · L. · Driessen · M. M. G. · Gerritsma · Y. H. · Bolton · C. · Da Silva · C. · Kocks · J. W. H.
Objective

To explore the impact of acute worsening events (AWEs), defined as clinically relevant deteriorations in peak expiratory flow, reliever use and/or symptoms, on patients’ daily lives and identify behaviours linked to their recognition and management.

Design

A qualitative international substudy was conducted in the Netherlands, Spain, the USA, Canada and the UK (2023–2024).

Participants

19 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) from a randomised clinical trial participated. Interviews, triggered by AWEs and repeated 6 weeks later, were audio-recorded, transcribed and analysed.

Results

Patients varied in identifying bad days, reporting inability to perform physical activities, symptom worsening or the need for add-on treatment. Recognition of AWEs depended on their duration: shorter events (

Conclusions

AWEs significantly impact daily life but vary widely in recognition and thresholds for seeking care. Limited awareness of daily disease variations may contribute to both under-reporting of worsening events to healthcare providers and suboptimal self-management in COPD.

Trial registration number

NCT05492877.

Simulation and the Translation Into Clinical Practice of Nursing Students' Clinical Judgement, Knowledge of the Nursing Process and Self‐Confidence: A Mixed Methods Randomized Controlled Study

ABSTRACT

Aims

To evaluate the effectiveness of simulation on nursing students' translation into practice of clinical judgement, knowledge about the nursing process self-confidence and to comprehend the learning process and translation into clinical practice of competencies developed through clinical simulation in nursing students.

Design

Two-arm, experimental, randomized controlled study designed using the explanatory sequential mixed method with qualitative step anchored in grounded theory.

Methods

Eighty undergraduate nursing students were allocated in practice groups and the groups were randomly assigned to an experimental (simulation; n = 39) or control group (study case; n = 41) and, after the intervention, participated in 3-day clinical practice activities and were assessed regarding clinical judgement, knowledge of the nursing process and self-confidence. Students in the experimental group were invited to focus groups.

Results

Seventy-six students were analysed. The findings showed the effectiveness of simulation combined with clinical practice in the development and translation of clinical judgement (β = 5.03; p = 0.001) and knowledge of nursing process (β = 2.20; p < 0.001). There was no difference regarding self-confidence. A grounded theory emerged with three categories related to consolidation of prior knowledge, translating competencies into clinical practice and application of these competencies in nursing care that explain the theoretical category ‘learning and translating into clinical practice’.

Conclusion

Findings suggest that simulation combined with clinical practice can effectively enhance nursing students' clinical judgement and knowledge of the nursing process, facilitating the translation of these competencies into real-world practice. The qualitative findings suggest that simulation promotes meaningful learning and supports the practical application of nursing competencies.

Implications for Nursing Education

This study supports the integration of simulation into nursing curricula to enhance clinical judgement and nursing process competencies. By promoting meaningful learning and facilitating knowledge transfer to clinical settings, simulation prepares students for real-world decision-making and strengthens the quality and safety of nursing care delivery.

Patient or Public Contribution

No patient or public contribution.

Registration

RBR-7v374c6 (Brazilian Clinical Trials Registry) https://ensaiosclinicos.gov.br/rg/RBR-7v374c6

Lower Limb Symmetry Index in Cavus and Normal Feet by Means of a Baropodometric Platform: A Case–Control Study

ABSTRACT

High-arched feet affect approximately 10%–15% of the general population. Although the relationship between plantar pressure and bilateral symmetry is well studied, there is limited evidence regarding the use of Symmetry Index and pressure platforms. The objective of the study is to compare dynamic foot pressures and Symmetry Index during gait between subjects with Pes Cavus and subjects with normal feet. The analysis of asymmetric pressure patterns could benefit from studies that compare dynamic foot pressures and Symmetry Index values in subjects with high-arched feet and normal feet. This analysis can promote better clinical understanding of gait alterations and help solve biomechanical problems that may lead to pathologies, as well as prevent and treat them. A descriptive case–control study was developed from October to December 2024 with 82 participants, 41 with Pes Cavus and 41 normal feet and 71 females of 25.52 ± 5.99 years through a consecutive nonrandom technique. For this study, a baropodometry platform (Neo-Plate, Herbitas) was used, which acquired dynamic gait with a 2-step protocol. The inclusion criteria regarding the selection of subjects were age 18–65 years; if both cavus feet, Navicular Drop Test (NDT) < 9 mm; neutral feet and no lower limb problem or surgery. Regarding SI use, the PC demonstrated to have large asymmetries compared to the control group. Left anterior pressure was lower (44.93% ± 4.59% vs. 48.60% ± 3.43%, p = 0.014), left posterior pressure was higher (55.07% ± 4.58% vs. 51.40% ± 3.43%, p = 0.013) and the left Initial Contact Phase (ICP) was prolonged (123.34 ± 51.75 ms vs. 91.30 ± 31.86 ms, p = 0.036); right medial pressure was higher (58.18% ± 4.08% vs. 53.77% ± 4.79%, p = 0.034). SI measurements were greater in normal foot group than in the PC group with SI 94.15% ± 5.00% versus 93.75% ± 4.59%, p = 0.001, respectively; ICP and lateral SI were both p = 0.001. Findings confirmed that subjects with cavus feet tend to present greater alterations in bilateral symmetry, specifically posteromedial pressure movements and altered gait phases, which are indicative of more probability of future injuries. For this reason, pressure platforms are excellent tools for understanding, analysing and therefore applying the correct treatment according to the SI.

Sensitivity of immunohistochemistry in the laboratory diagnosis of leprosy: a systematic review protocol

Introduction

Leprosy is a chronic disease caused by the bacillus Mycobacterium leprae and remains a public health concern in endemic countries. Early diagnosis is fundamental to prevent transmission and irreversible disabilities. Histopathological identification of acid-fast bacilli in tissue specimens is traditionally considered the laboratory reference standard; however, its sensitivity is limited, particularly in paucibacillary forms. Immunohistochemistry (IHC) has been proposed as an adjunctive diagnostic tool for detecting M. leprae antigens in tissue samples, but its diagnostic accuracy has not been systematically synthesised. This protocol outlines a systematic review aimed at evaluating the sensitivity and specificity of IHC in the laboratory diagnosis of leprosy.

Methods and analysis

This systematic review of diagnostic test accuracy studies will include analytical observational studies and clinical trials evaluating IHC in human subjects with suspected leprosy. The reference standard will be defined as the identification of acid-fast bacilli in skin biopsy specimens from patients with compatible clinical presentation using conventional staining methods (eg, Fite-Faraco), with the exclusion of alternative mycobacterial infections when applicable. Searches will be conducted in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, Web of Science and BVS/LILACS (Biblioteca Virtual em Saúde/Latin American and Caribbean Health Sciences Literature), as well as grey literature sources, at 31 May 2026. Two independent reviewers will perform study selection, data extraction using a standardised Microsoft Excel form and risk of bias assessment using the Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity estimates will be calculated. If appropriate, a bivariate random-effects meta-analysis will be conducted using RevMan (Review Manager) and Stata.

Ethics and dissemination

Ethical approval is not required because this study will use publicly available data. The results will be submitted to a peer-reviewed journal and presented at scientific conferences.

Social enrichment mitigates facial expressions and physiological indicators of short-term stress in horses

by Ana Caroline Bini de Lima, Vanessa Cristini Sebastião da Fé, Maria Simara Palermo Hernandes, Emily Caroline Pfeifer de Cristo, Ana Gabrieli dos Santos Fagundes Euzébio, Maria Vitória e Silva Sousa, Fabiana Ribeiro Caldara, Viviane Maria Oliveira dos Santos

This study aimed to evaluate the ability of social noncontact environmental enrichment to facilitate social buffering and to characterize the emotional experience of horses subjected to restraint in stock by assessing physiological parameters and facial expressions. Pantaneiro horses (n = 11) were evaluated in a crossover design with two treatments: social noncontact enrichment during stock restraint and social isolation during stock restraint. Physiological parameters (heart rate, heart rate variability, respiratory rate, ocular temperature by infrared thermography, and auricular temperature by infrared thermometer) and facial expressions (EquiFACS) were assessed throughout the 24-minute restraint period. When horses were accompanied by a conspecific, heart rate, respiratory rate, and eye temperature were lower (p nostril dilator (AD38), inner brow raiser (AU101), upper eyelid raiser (AU5), eye white increase (AD1), ears forward (EAD101), and ears back (EAD104), was also lower (p 

Clinical Trials in Central Venous Access Devices: An Evidence and Gap Map

ABSTRACT

Aims

To systematically map the landscape of central venous access device research from 2014 to 2024, identifying critical gaps in evidence that may impact nursing practice and patient outcomes across the full device lifecycle from selection through to removal.

Design

This review was conducted in accordance with the Guidance for producing a Campbell evidence and gap map and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Data Sources

PubMed, Cumulative Index to Nursing and Allied Health Literature Complete, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched with additional hand-searching of reference lists from included reviews.

Methods

We systematically reviewed literature published between 2014 and 2024, mapping 710 studies on central venous access device interventions and outcomes. Studies were categorised by design, population, setting, device characteristics, intervention types, and outcomes. Evidence was evaluated using the National Health and Medical Research Council levels of evidence framework.

Results

Of 710 included studies, 89 were systematic reviews and 621 primary studies, of which 41.1% (n = 292) were randomised controlled trials. Research was primarily conducted in high-income countries (n = 405, 65.2%) and focused on adults (n = 370, 59.6%) in hospital inpatient settings (n = 588, 94.7%). Catheter insertion and infection prevention dominated the evidence base, while device selection and removal procedures were less studied. Infection outcomes were extensively reported (bloodstream infection: n = 455, 13.6% of 3349 outcomes), while patient-reported outcomes (n = 218, 6.5%) and cost (n = 60, 1.8%) were underrepresented.

Conclusions

This review reveals that central venous access device research is predominantly focused on insertion and infection prevention while other key parts of nursing practice are under-supported.

Implications for the Profession and/or Patient Care

Future nursing research should address these gaps to improve evidence-based care across diverse populations and healthcare contexts, particularly focusing on understudied device types, settings, and vulnerable populations.

Reporting Method

This review was conducted and reported in accordance with the Guidance for producing a Campbell evidence and gap map.

Patient or Public Contribution

This study did not include patient or public involvement in its design, conduct, or reporting.

Safe Mobility in Hospitalised Older Adults: A Concept Analysis

ABSTRACT

Aim

To conduct a concept analysis of ‘safe mobility’, with specific application in hospitalised older adults, identifying its defining attributes, antecedents and consequences.

Background

The promotion of safe mobility is essential for maintaining the functionality of hospitalised older adults. However, this idea is not yet clearly defined in the scientific literature, requiring a conceptual analysis for better understanding and applicability in nursing practice.

Design

Concept analysis.

Methods

The concept analysis methodology of Walker and Avant was employed, consisting of eight steps. Sources from the scientific literature (BDENF/VHL, Scopus, CINAHL/EBSCO, Embase, Web of Science, PEDro, MEDLINE/PubMed and CAPES Thesis and Dissertation Catalogue, as outlined in a scoping review previously published by the authors) and terminologies from dictionaries and nursing practice, such as SNOMED CT, ICNP, NANDA, NIC and NOC, were analysed.

Results

The concept of ‘safe mobility’ does not have a consolidated definition but was identified through three defining attributes: active movement, prevention of fall-related harm and prevention of immobility-related harm. The antecedents include the older adults' conditions, adaptation of the hospital environment, training of the multidisciplinary team, patient behaviour and family involvement. The consequences involve the maintenance of functionality, improvement of quality of life, reduction of hospital length of stay and costs, as well as a decrease in rates of readmission, referrals to long-term care institutions and mortality.

Conclusion

The concept analysis revealed that safe mobility involves promoting active movement and preventing harm related to both immobility and falls.

Implications for the Profession and Patient Care

Strategies based on this concept can improve the quality of life of older adults, reduce complications and optimise hospital costs.

No Patient or Public Contribution

This concept analysis examines existing literature and does not require patient-related data collection. The methodological approach does not necessitate collaboration with the public.

Isolated and Combined Effects of Sedentary Behaviour and Physical Activity on Muscle Strength in Older Adults: A Prospective Cohort Study

ABSTRACT

Aim

We aim the isolated and combined effects of sedentary behaviour exposure time and physical activity levels on muscle strength in older adults.

Design

This prospective observational cohort study, analytical in nature, using exploratory survey methods and physical performance testing. With 5-year longitudinal follow-up (2015–2020).

Methods

A total of 459 older adults participated in the baseline, with a total of 224 being included/located again in the follow-up. We evaluate muscle strength using handgrip tests and sit-to-stand tests. The international physical activity questionnaire was used to measure physical activity and sedentary behaviour. Generalised Estimation Equations tested both independent and combined effects, reporting results as β coefficients and confidence intervals.

Results

Older adults exhibiting low sedentary behaviour displayed enhanced handgrip strength compared to those with high sedentary behaviour. Notably, older adults who were sufficiently active with low sedentary behaviour, sufficiently active with high sedentary behaviour, and insufficiently active with low sedentary behaviour showed increased handgrip strength compared to their counterparts who were insufficiently active with high sedentary behaviour. This trend was consistent for lower limb strength.

Conclusion

Interventions that encourage a reduction in sedentary behaviour and an increase in physical activity are essential to maintain muscle strength among older adults.

Implications for Practice

The findings of this study underscore the importance of addressing both sedentary behaviour and physical activity levels in clinical interventions aimed at preserving muscle strength in older adults. Routine assessments of physical activity and sedentary behaviour could help tailor personalised exercise programs, potentially enhancing functional independence and reducing the risk of frailty and disability in older patients.

Patient or Public Contribution

Patients were involved in the sample of the study.

Reporting Method

This study was conducted in accordance with the Strengthening Research in Observational Studies in Epidemiology (STROBE) guidelines.

Recommendations for Arterial Blood Gas Collection in Intensive Care: Scoping Review

ABSTRACT

Objectives

To map and synthesise the main recommendations for arterial blood gas (ABG) collection in intensive care units (ICUs).

Design

A scoping review was conducted according to the PRISMA-ScR Checklist, supported with The PAGER framework and guided by the Joanna Briggs Institute methodology to ensure methodological rigour and analytical comprehensiveness.

Methods

Data collection was conducted from February to April 2024. The data sources included: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, PubMed Central, Scientific Electronic Library Online (SciELO), Web of Science (WoS), SCOPUS, Science Direct, Virtual Health Library (VHL), Excerpta Medica database (Embase), CAPES Thesis and Dissertation Catalogue, Brazilian Digital Library of Theses and Dissertations (BDTD), Scientific Open Access Repository of Portugal (RCAAP), Theses Canada and the Oswaldo Cruz Foundation (Fiocruz) repository.

Results

Key findings recommend the radial artery as the preferred puncture site, an insertion angle of 30° to 45°, the use of 1 or 3 mL syringes and 20G or 23G gauge needles. Transport and storage at room temperature are advised. Cryoanalgesia and subcutaneous analgesia methods were found to be effective for pain management.

Conclusion

The review highlights the best practices for arterial blood gas collection in critical care. The synthesized evidence strengthens clinical practice, informs guidelines for intensive care nursing and promotes safer, higher-quality care for critically ill patients.

Implications for the Profession and/or Patient Care

The evidence-based recommendations identified can enhance nursing care related to arterial blood gas collection. Adherence to these practices promotes safer, more humanised and evidence-based care during the procedure.

Reporting Method

The report of this study followed the PRISMA-ScR Checklist.

Patient or Public Contribution

There was no patient or public involvement in this scoping review.

Prospective cohort study of TIMP-1 and myocardial fibrosis in Chagas disease at a reference clinic in Pernambuco, Brazil: PTICH trial protocol

Por: Martins · S. M. · Macedo · C. T. · Meira · C. S. · Paim Santos · L. H. · Larocca · T. F. · Cavalcanti da Silva · F. F. · Leandro Lira · C. N. · da Silva · I. P. M. · De Araujo · L. T. · Soares · M. B. P.
Background

Chagas disease affects millions of individuals across Latin America and imposes a substantial economic burden on healthcare systems, particularly in rural and underserved regions. Chronic Chagasic cardiomyopathy remains one of the leading causes of heart failure-related mortality in endemic countries. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a potential biomarker of myocardial fibrosis in cardiomyopathies. This study was designed to investigate the association between TIMP-1 and myocardial fibrosis in chronic Chagas disease and to assess its potential as an early biomarker of fibrotic remodelling.

Methods and analysis

Bottom of form: The PTICH trial is a single-centre, prospective observational cohort study conducted at a government reference clinic in Pernambuco, Brazil. The study aims to enrol 210 adults with Chagas heart disease: 140 without ventricular dysfunction (left ventricular ejection fraction (LVEF) ≥52% in women and ≥54% in men) and 70 with ventricular dysfunction (LVEF

Ethics and dissemination

The Research Ethics Committee (REC) of Chagas disease and heart failure outpatient clinic—PROCAPE approved the PTICH trial (CAAE number: 65746322.8.1001.5192). Written informed consent has been obtained from all participants enrolled to date, and data handling is in compliance with applicable privacy and data protection regulations. Study findings will be disseminated through targeted outreach to civil society, the scientific community, healthcare professionals and Brazilian Unified Health System (SUS) policymakers; school-based science communication activities conducted in collaboration with state education departments (potentially including oral health educational materials); policy briefs and targeted reports for public health managers; technical meetings and institutional presentations; a plain-language summary published on the institutional website; and submissions to peer-reviewed journals and presentations at academic and health policy conferences.

Trial registration number

RBR-3dcrj98.

The effects of increasing dosages of narasin on ruminal fermentation patterns, bacterial community composition, and nutrient digestibility in beef cattle receiving feedlot diets

by Ana Laura Januário Lelis, Leandro Aparecido Ferreira da Silva, Daniel Moretto Casali, Tiago Leiva, Murilo Chuba Rodrigues, José Paulo Roman Barroso, Pedro Veloso Facury Lasmar, Camila Lisboa Tomaz, Anabelle Jorge Barbosa, Camila Cesario Fernandes Sartini, Johnny Maciel de Souza, Danilo Domingues Millen

This study evaluated the effects of increasing narasin doses on ruminal fermentation, nutrient digestibility, ruminal pH stability, papillae histology, and microbial composition in Angus cattle fed feedlot diets. Three rumen-cannulated Angus steers (average body weight: 680 kg) were assigned to a 3 × 3 Latin square design and received diets containing 13, 20, or 27-ppm of narasin. Each experimental period consisted of 14 days of adaptation followed by seven days of sampling. Ruminal degradability was assessed on days 15–17, apparent digestibility on days 15–19, continuous ruminal pH on days 19–20, and samples for short-chain fatty acids (SCFA), microbiota, and ruminal histology were collected on days 20 and 21. Ruminal degradability was not affected by narasin dose. Digestibility of acid detergent fiber (ADF) was significantly influenced, with the greatest values observed at 27-ppm (P = 0.01). Increasing narasin doses improved ruminal pH stability, as indicated by a linear increase in minimum pH (P = 0.01) and a reduction in the duration of pH below 5.6 (P = 0.10). At 13 ppm, SCFA production, particularly acetate and propionate, increased (P P P = 0.02), and butyrate (P P P = 0.03). Narasin supplementation altered ruminal microbial composition, increasing the relative abundance of Lachnospiraceae and Isotricha while reducing lactic acid–producing bacteria. In terms of ruminal morphology, supplementation with 20-ppm of narasin increased the keratin layer thickness of ruminal papillae (P = 0.02), suggesting enhanced epithelial development. Overall, narasin supplementation modulated ruminal function and microbial ecology, with doses between 13 and 20-ppm providing the most favorable balance between fermentative efficiency and ruminal health in feedlot cattle.

Nursing Doctoral Theses Across Eight Countries: A Document‐Based Qualitative Study

ABSTRACT

Background

Doctoral research in nursing is central to advancing scientific knowledge, strengthening professional identity, and informing evidence-based practice, education, and health policy. Analyzing the thematic content of doctoral theses offers insight into research priorities and national variations in nursing scholarship. Yet, no systematic cross-country analysis has examined the thematic focus of such work.

Objective

To explore and describe the diversity and scope of doctoral nursing research themes across eight countries in the Sigma Europe Region, identifying key areas of scholarly focus and shared priorities.

Design

A document-based qualitative study using reflexive thematic analysis, as outlined by Braun and Clarke, to examine patterns of meaning within thesis summaries.

Participants and Setting

The study included doctoral nursing thesis summaries defended between January 2020 and December 2023, sourced from national and institutional repositories in eight countries of the Sigma Europe Region. A total of 15 repositories (4 national, 11 institutional) were systematically searched, and additional summaries were obtained via direct contact with universities offering doctoral nursing programmes.

Methods

Data were collected between September 2024 and February 2025 using predefined inclusion and exclusion criteria. In total, 431 eligible thesis summaries were analyzed following Braun and Clarke's six-phase framework, supported by MAXQDA software for data management and coding.

Results

Thematic analysis identified three overarching domains: (1) foundations of nursing practice and care philosophy, (2) systemic and organizational dimensions of nursing, and (3) clinical innovation and public health impact. Ten interrelated themes emerged, including holistic and patient-centred care; emotional, psychological, and quality-of-life dimensions; communication in healthcare; workforce challenges; transforming nursing practice; maternal, neonatal and pediatric health; digital and virtual health innovations; public health and chronic disease management; and disease management, caregiving, and outcomes. Cross-cutting elements such as cultural sensitivity and resilience spanned multiple themes.

Conclusion

This cross-national synthesis demonstrates the breadth and depth of doctoral nursing research in the Sigma Europe Region. Findings highlight nursing's pivotal role in addressing healthcare needs through innovative, person-centred, and evidence-informed solutions, and underscore the value of international collaboration in shaping resilient, equitable, and future-ready healthcare systems.

Cluster randomised controlled trial for service delivery redesign of primary care for people with diabetes: study protocol

Por: Mazzoni · A. · Roberti · J. · Guglielmino · M. · Jorro-Baron · F. · Mazzaresi · Y. · Falaschi · A. · Alvarez · J. · Gibbons · L. · Leslie · H. H. · Silva · C. · Garcia · P. J. · Garcia-Elorrio · E.
Introduction

Strong primary healthcare enhances resource efficiency and resilience. Type 2 diabetes poses a growing global health challenge, with Argentina’s healthcare system struggling to detect and manage the disease effectively. Many patients bypass primary healthcare for secondary facilities, undermining continuity of care and increasing costs. Following a diagnostic process in collaboration with policymakers, we propose evaluating a redesigned primary care model consisting of codesigned evidence-based implementation strategies to improve type 2 diabetes management in Mendoza, Argentina.

Methods and analysis

This is an efficient, parallel-arm cluster randomised controlled Hybrid Type II trial with 12 clusters (administrative areas with 2–3 health facilities) allocated 1:1 to control (usual care) or intervention. In phase I, we will codesign, pilot and refine an implementation strategy package. In phase II, we will conduct the trial: 9-month baseline data collection, 15-month intervention and 6-month sustainability period. We will enrol a cohort of 396 patients with type 2 diabetes at primary healthcare centres and follow them for 12 months during the intervention and 6 months sustainment using routine clinical records and patient surveys. In phase III, we will conduct analysis, report and disseminate findings. The primary outcome will be a composite outcome including glycaemic control (glycated haemoglobin (HbA1c)

Ethics and dissemination

All study activities will comply with national and international ethics guidelines, presenting minimal risk to participants. The protocol was submitted and approved by the local independent ethics committee at the Mendoza Ministry of Health (Consejo Provincial de Evaluación ética en investigación en Salud-Provincial Health Research Ethics Review Board, Reference number: 149/2024). Facility-level permission will be obtained for participation and sharing of deidentified data. Written informed consent will be required from study participants, who will receive information on the study’s purpose, procedures, risks and benefits. Dissemination activities and outputs will include writing and submitting manuscripts for publication; writing policy briefs to support strategy implementation in other regions or countries; and tailoring outputs for patients, clinicians and researchers. We anticipate that improvements in disease management and patient experience will have clinical and economic benefits related to reduced usage of secondary-level and tertiary-level facilities, lower cost per visit and a reduced number of clinical events related to diabetes.

Trial registration number

ISRCTN63277390.

Reduced levels of mitochondrial ribosomal protein <i>MRPL54</i> does not alter Apc related adenoma formation

by Claudia N. Spaan, Eileen Daniels, Wouter L. Smit, Ruben J. de Boer, Joana Silva, Jacqueline L. M. Vermeulen, S. Meisner, Vanesa Muncan, Riekelt H. Houtkooper, Jarom Heijmans

Reprogramming of energy metabolism is one of the hallmarks of cancer cells and mutations that modify wild type intestinal cells to colon carcinomas increases cellular energy expenditure. Mitochondria are the main site for ATP production in (cancer) cells and disrupting their function results in impaired tumor forming efficacy. The mitochondrial ribosomal proteins (MRPs) constitute the ribosome specifically in mitochondria, and as such are crucial for the translation process of the electron transport chain complex subunits. We hence aimed to explore the consequence of reduced MRP expression on adenomagensis and investigate this in a genetic mouse model with bodywide heterozygosity for Mrpl54. We show that Mrpl54 heterozygosity does not alter adenoma formation, intestinal proliferation or apoptosis in a heterozygous Apc model. Furthermore, diminished Mrpl54 expression did not decrease stemness or global parameters of metabolism in colorectal cancer cell lines.

Technologies in Intensive Care Therapy and the Obstacles in Nursing Practice: Systematic Review

ABSTRACT

Aim

To identify obstacles faced by nurses when using health technologies in Intensive Care Units (ICUs).

Design

Systematic review following PRISMA and registered in PROSPERO.

Methods

Six databases were searched. Two reviewers independently screened studies and appraised methodological quality using the Joanna Briggs Institute tool. Data were synthesized narratively.

Results

Eight studies met eligibility criteria. Barriers clustered around limited training and technical competence, shorter professional experience, increased workload with multiple devices, organizational culture, and reduced direct patient contact, which may undermine patient-centered care. Heterogeneity of study designs precluded meta-analysis.

Conclusions

Obstacles to technology use in ICUs arise from individual and organizational factors. Addressing these barriers requires structured education, mentoring for novice nurses, workload management, and supportive policies that integrate technology without displacing bedside care.

Linking Evidence to Action

Nursing leaders and educators should implement ongoing, ICU-specific technology training and mentoring. Managers and policymakers must ensure adequate staffing and promote Health Technology Assessment to align device implementation with clinical needs, safeguarding patient safety and the human dimensions of care.

Persistence of the hepatic benefits of high-intensity interval training (HIIT) during detraining despite body weight regain in mice

by Renata dos Santos Guarnieri, Guilherme Sá de Oliveira, Kaylaine Marques Ferreira, Aline Penna-de-Carvalho, Vanessa Souza-Mello, Sandra Barbosa-da-Silva

High-intensity interval training (HIIT) is an effective intervention for improving metabolic health and mitigating metabolic dysfunction-associated steatotic liver disease (MASLD). Nonetheless, the stability of these benefits throughout detraining periods and upon weight regain remains inadequately characterized. This study aimed to evaluate whether hepatic improvements induced by HIIT are sustained during detraining, even after body weight regain. Eighty male C57BL/6 mice were fed either a control (10% fat) or a high-fat (HF) diet (50% fat) for 12 weeks. Following this period, the animals were allocated to groups subjected to continuous HIIT or intermittent training cycles (each lasting 3 weeks). The outcomes assessed included body mass (BM), glucose tolerance, lipid profiles, liver enzyme levels (aspartate aminotransferase and alanine aminotransferase), hepatic steatosis, and the expression profiles of genes associated with lipogenesis (Srebf1, Mlxpl, and Fas), β-oxidation (Ppara and Cpt1a), and endoplasmic reticulum (ER) stress (Atf4, Ddit3, and Gadd45). Compared with the sedentary HF-NT condition, continuous HIIT reduced BM and improved glucose tolerance. Intermittent training (HF-TNT, HF-NTN) preserved metabolic benefits and reduced triglyceride and cholesterol levels. Notably, hepatic steatosis was significantly alleviated in all training groups but persisted even after detraining. Additionally, HIIT downregulated the expression of lipogenic genes and upregulated the expression of genes involved in β-oxidation. The levels of markers indicating ER stress were attenuated by HIIT, with a sustained reduction during periods of detraining. HIIT-induced metabolic and hepatic improvements persist partially during detraining, despite weight regain. These findings underscore the therapeutic value of continued or periodically repeated physical training in mitigating the adverse effects of an HF diet and preventing the progression of metabolic disorders such as MASLD.
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