<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.

Determinant Factors of Self‐Care Deficit in People With Chronic Wounds: A Scoping Review

ABSTRACT

Aims

To identify and synthesise the scientific evidence on determinants of self-care deficits in people with chronic wounds.

Design

Scoping review based on the Joanna Briggs Institute guidelines.

Methods

This scoping review was conducted by a review team responsible for study screening, data extraction and synthesis. The categorisation of findings was grounded in Orem's Self-Care Deficit Theory and operationalised using the COM-B model and the Theoretical Domains Framework.

Data Sources

A comprehensive search, without date or language restrictions, was conducted in Web of Science, MEDLINE (PubMed), Cochrane Library, Scopus (Elsevier), SciELO, Ovid and EMBASE (Elsevier), from November 2023 to April 2024.

Results

Of the 3076 records identified, 22 studies were included. Most were cross-sectional studies, with sample sizes ranging from seven to 1085 participants and a mean age of 61.45 years, predominantly involving people with venous leg ulcers and diabetic foot ulcers. Findings were synthesised into four categories: clinical, socioeconomic, behavioural and health system-related factors, indicating that multiple interrelated determinants influence engagement in self-care and contribute to persistent self-care deficits.

Conclusion

The findings demonstrate the vulnerability of people living with chronic wounds, arising from the complex interaction of clinical, psychosocial, socioeconomic and health service-related factors that determine self-care deficits. These deficits compromise wound healing, prolong treatment and negatively affect quality of life, underscoring the need for person-centred approaches to care.

Implications for the Profession and/or Patient Care

This study reinforces the need for integrated and sustainable models of care grounded in person-centred practice, aimed at strengthening self-care capacities, enhancing clinical practice and informing more equitable health policies.

Impact

This review highlights the multifactorial nature of self-care deficits in people with chronic wounds. Nursing plays a key role in identifying barriers and strengthening capacities through Orem's supportive–educative system. Person-centred interventions improve adherence and continuity of care.

Reporting Method

This review follows the PRISMA guidelines for reporting.

Patient or Public Contribution

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

Occupational exposure to cadmium: protocol for a scoping review

Introduction

Cadmium is a metal that poses significant health risks, particularly in occupational environments where exposure can happen. The main objective of this scoping review is to review the cadmium exposure levels in the different occupational settings in the European Union (EU), considering the regulatory measures currently in place. The secondary objectives, depending on the availability of data, are (a) to identify the occupational settings where higher exposure levels occur, (b) to identify any geographical and temporal differences and trends within the EU and (c) to identify the most relevant co-exposures reported.

Methods and analysis

A scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews reporting guidelines. Studies reporting quantitative occupational data on cadmium exposure obtained through human biomonitoring and/or air monitoring will be included. A descriptive analysis of the findings will be performed.

Ethics and dissemination

This protocol for a scoping review does not require ethical approval as it is based on secondary data. The dissemination plan of the scoping review includes its publication in a scientific journal of reference, as it is expected that it will provide important knowledge to support ongoing and future occupational health interventions in the EU, at the technical and regulatory levels.

Registration

This study is registered at the Open Science Framework (OSF), 7 April osf.f2w3h.

Evaluación y cuidado de la piel al final de la vida

Este artículo contempla una actualización con base a los diez puntos establecidos por el consenso Skin Changes at the Life's End [Cambios en la Piel en el Final de la Vida] (Scale, por su sigla en inglés) y tiene por objetivo discutir la evaluación de las condiciones y el cuidado de la piel en el final de la vida. Acerca de los pacientes y familiares, se propone la construcción de un plan de cuidados basándose en sus deseos que deben ser debidamente registrados. Para los profesionales de salud, las recomendaciones buscan la educación para la evaluación de los signos clínicos de falla e insuficiencia de la piel. Así pues, la prioridad es la comodidad del paciente. Se concluye que la utilización del consenso Scale va al encuentro de la filosofía de los cuidados paliativos y puede así mejorar los aspectos multidimensionales involucrados en la calidad del proceso de morir.