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Burn Wound Infections With Staphylococcus aureus: Clinical Characteristics and Risk Factors for Methicillin‐Resistant Strains

ABSTRACT

This study aimed to systematically delineate the clinical characteristics and identify the key risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) infections in burn patients, thereby informing targeted preventive measures and therapeutic strategies. This retrospective study included 270 burn patients with Staphylococcus aureus (S. aureus) infections at a Chinese centre (2019–2022), comprising 127 MRSA and 143 methicillin-susceptible S. aureus (MSSA) cases. Clinical data were analysed to assess infection profiles, resistance patterns and MRSA risk factors. Amongst the infections, 68.1% (184/270) were caused by multi-drug resistant S. aureus, specifically 47.0% (127/270) by MRSA and 21.1% (57/270) by MSSA. The predominant resistance pattern (penicillin, oxacillin, gentamicin, clindamycin, erythromycin, ciprofloxacin, levofloxacin, tetracycline) accounted for 23.9% (44/184) of multidrug-resistant cases. The overall MRSA detection rate was 47.0% (127/270). Univariate analysis identified multiple factors significantly associated with MRSA infection (p < 0.05). Multivariate analysis identified the use of ≥ 3 types of antibiotics as an independent risk factor for MRSA infection in burn wounds. The detection rate of multi-drug resistant S. aureus (including MRSA) infections in burn wounds is relatively high. A number of variables are the influencing factors for MRSA infections. Medical personnel should adopt infection control measures to block the transmission of multi-drug resistant bacteria (including MRSA).

Incidence and Severity of Nurse‐Sensitive Adverse Events in Older Adults After Physical Trauma: A Medical Record Review

ABSTRACT

Aim

This study aimed to investigate the incidence and characteristics of nursing-sensitive adverse events (NSAEs) in older adults (≥ 65 years) hospitalised with traumatic injuries, and to explore associations with frailty, demographic factors, injury characteristics and hospital-related factors.

Design

NSAEs were identified through a retrospective medical record review of a prospectively collected cohort.

Methods

Patients ≥ 65 years admitted with physical trauma to a Swedish level I trauma centre between 2020 and 2024 were included. NSAEs were identified using a modified trigger tool chart review. Descriptive statistics were used to determine the incidence and characteristics of NSAEs in the whole cohort. Group differences, associations and predictors were examined using exact, non-parametric, or logistic regression methods.

Results

A total of 270 trauma patients ≥ 65 years were included, of whom 25.6% had experienced at least one NSAE. The overall incidence was 38.2 events per 100 admissions, with hospital-acquired infections being the most common type of NSAE (16.7%), followed by overdistended bladder (6.3%) and pressure injuries (5.6%). Frailty and length of hospital stay were associated with an increased likelihood of NSAEs, with hospital length of stay emerging as the strongest predictor in multivariable analysis.

Conclusion

NSAEs are common among older trauma patients and are associated with frailty, injury characteristics and length of stay. Improving early risk identification and ensuring timely preventive nursing care may enhance patient safety in this vulnerable population.

Implications for the Profession and/or Patient Care

The findings highlight the important role of nursing in the care of older trauma patients and the need for consistent delivery of fundamental nursing care. Strengthening clinical practices that support early identification of high-risk patients and the timely implementation of preventive interventions may improve patient safety and outcomes in this vulnerable population.

Impact

This study addresses the knowledge gap regarding NSAEs in older trauma patients, a population with increased vulnerability to adverse outcomes. The findings provide insights into the occurrence and risk factors of NSAEs in this group and highlight the importance of translating risk assessment into effective clinical action. These results may inform clinical practice and support the development of strategies to improve patient safety in trauma care for older adults.

Reporting Method

This study was informed by the Standard Elements in Studies of Adverse Events and Medical Error (SESAME). The completed SESAME checklist is provided in the Supporting Information S1.

Patient or Public Contributions

No patient or public contributions.

Identifying Barriers and Facilitators to Providing Psychologically Safe Care in Inpatient Mental Healthcare. A Theoretical Domains Framework‐Informed Qualitative Study

ABSTRACT

Aim(s)

To explore the facilitators and barriers to staff providing psychologically safe care in inpatient mental healthcare when restrictive practices are used.

Design

Qualitative descriptive interview study.

Methods

Twenty semi-structured interviews were conducted with staff with experience working in inpatient mental healthcare in England. Analysis included principles of framework analysis, informed by the Theoretical Domains Framework.

Results

Access to resources and a safe environment for both patients and staff were recognised as important (environmental context and resources) but access was impacted by competing organisational priorities and expectations (beliefs about capabilities). Participants recognised knowledge gaps in themselves and their colleagues (knowledge). Being able to confidently make decisions about risk was seen as central to the staff role (social/professional role and identity). Collaboration between staff is needed to make positive change and progression towards psychologically safe care (social influences). Empathy and compassion were driving factors in participants trying to use psychologically informed alternatives, but burnout hindered this (emotions).

Conclusion

Ensuring that staff feel supported in their role to implement psychosocial informed alternatives to restrictive practices, as well as providing safe environments for both patients and staff, could support the integration of psychologically safe care on inpatient mental health wards.

Implications for the Profession and/or Patient Care

Key facilitators and barriers to staff providing psychologically safe care are identified to support practice and improvements to patient care.

Reporting Method

Consolidated criteria for reporting qualitative studies (COREQ).

Patient or Public Contribution

Former patients and members of the public were involved in the conceptualisation of key concepts and design of this study.

Parenting Stress and Nurse Workforce Sustainability: An Integrative Literature Review

ABSTRACT

Background

Parenting stress among clinical nurses has been associated with turnover-related outcomes. For many nurses, critical periods of career development and accumulated clinical responsibility overlap with reproductive and early parenting years. Features of nursing work may shape parenting stress through demands related to scheduling, workload, and limited flexibility.

Design

Integrative literature review.

Methods

An integrative literature review was conducted following the methodological framework of Whittemore and Knafl. The final searches across three databases (CINAHL Complete, Medline, and Embase) were completed on May 14, 2026. Eligible articles were published in English, addressed parenting stress, and, when empirical, included nurses as a distinct population. Reporting followed PRISMA guidelines.

Results

Eight articles met all inclusion criteria. Countries of origin included South Korea, Turkey, and China. Approximately 1667 nurse-parent participants were represented across the included studies. Main themes included as follows: (1) Work-Family Role Conflict and Parenting Stress, (2) Parenting Stress Across Career and Family Life Stages, (3) Parenting Stress and Nurse Workforce Outcomes, and (4) Organizational and Structural Contributors to Parenting Stress.

Conclusion

Parenting stress appears to be a relevant nursing workforce issue shaped by structural conditions of practice. The structure and demands of patient care may intensify parenting stress. Additional research is needed to examine the effects of parenting stress in clinical nurses and the implications for nurse retention.

Implications

Organizational and policy-level interventions (including family-friendly scheduling, accessible childcare, and structured peer support programs) may support workforce sustainability among nurse-parents.

The European Parliament's Vote on the EU Health Workforce INI Report: An EFN Commentary

ABSTRACT

Aim

To discuss the implications of the European Parliament’s vote on the Own-Initiative Report (INI) on the EU Health Workforce for nursing policy, workforce sustainability and healthcare systems across Europe.

Design

Critical commentary.

Methods

Critical analysis of the European Parliament’s INI Report on the EU Health Workforce, informed by nursing workforce policy priorities and existing evidence on workforce sustainability, patient safety and professional development.

Results

The INI Report provides important political support for key nursing priorities, including safe staffing levels, advanced practice nursing, implementation of the Professional Qualifications Directive, ethical recruitment, occupational health and safety, workforce investment, preparedness and co-created digitalisation. The report highlights the importance of strengthening workforce sustainability and improving patient safety across the European Union.

Conclusion

The European Parliament’s recommendations represent a significant opportunity to advance nursing workforce policy at EU level. However, translating these recommendations into effective legislative and operational measures will require sustained political commitment, investment and implementation across Member States.

Staff Perspectives on Non‐Routine Compression Therapy for Inpatients With Venous Leg Ulcers: A Qualitative Study

ABSTRACT

Compression therapy is the evidence-based treatment for healing venous leg ulcers. However, it is not routinely applied in many UK hospitals. This paper explores hospital staff's' perspectives of venous leg ulcer care provision where compression therapy is not routinely applied. A semi-structured interview study was conducted with 11 participants, drawn from a larger study, who confirmed that their respective hospitals did not apply compression therapy to inpatients with venous leg ulcers. The interviews were analysed using reflexive thematic analysis. Findings indicate that venous leg ulcer care in hospitals was de-prioritised, which, along with structural and organisational constraints, affected clinicians' engagement and focus on it in their hospitals. This de-prioritisation also led to a lack of formal leg ulcer training in hospitals. However, some clinicians showed remarkable empathy for patients derived from their clinical professionalism and deep understanding of their suffering. To help hospital clinicians and senior managers prioritise venous leg ulcer care, it is crucial to first understand their clinical practise priorities. Secondly, understanding how some hospitals implement compression therapy could be beneficial for those where it is not routine practise. Further research should focus on better understanding clinicians and senior managers' clinical priorities and the structural and organisational constraints in real-world settings, ideally in hospitals where compression therapy is a routine practise. Most importantly, the study highlighted key questions for hospital leaders and policymakers: consider fostering the established clinicians' empathy before it is too late.

Understanding factors influencing HPV vaccine uptake among caregivers in Kwara State, Nigeria: A qualitative study

by Abdulmujeeb Opeyemi Muhammad-Olodo, Laura Asher

Introduction

Human papillomavirus (HPV) vaccine prevents over 90% of cervical cancers. In October 2023, Nigeria launched a free HPV vaccination campaign targeting girls aged 9–14 years. Despite removing cost barriers, misinformation about fertility impacts and population control contributed to variable uptake across states. Understanding caregiver decision-making is crucial for improving coverage. This study aimed to explore factors influencing caregivers’ HPV vaccination decisions during Nigeria’s 2023 campaign in Ilorin East Local Government Area, Kwara State.

Methods

A qualitative study using focus group discussions (FGDs) was conducted using purposive and snowball sampling. We recruited 41 caregivers (mean age 47 years; 71% female) of eligible girls from urban and rural communities. Five FGDs were conducted: four with vaccine acceptors (n = 35) and one with decliners (n = 6). Discussions were conducted in Yoruba, audio-recorded, transcribed verbatim, and analysed using Braun and Clarke’s reflexive thematic analysis. Ethical approval was obtained from two institutional review boards.

Results

Four themes emerged from the analysis. Trust operated at multiple levels: institutional (government programmes), interpersonal (healthcare worker competence), and community (religious/traditional leader endorsement). Historical medical mistrust, intensified by COVID-19 experiences, may have manifested as fertility and population control fears. Personal cancer experiences strongly motivated acceptance, whilst concerns about childhood sexuality influenced timing preferences. Despite free provision, barriers included geographic inequities (remote Fulani-Hausa communities were excluded), language barriers (no Hausa translators), school-based delivery gaps, and indirect costs (transport, time). Caregivers recommended house-to-house campaigns, multilingual services, traditional leader engagement, and permanent vaccination centres.

Conclusion

Free vaccine provision is necessary but not sufficient to ensure uptake. Successful HPV vaccination requires rebuilding trust through community engagement, addressing historical medical exploitation concerns, and ensuring equitable access. Integrating these findings into Nigeria’s National Programme on Immunisation could improve coverage from current estimates of 54% to targeted 90%, protecting more girls from cervical cancer whilst respecting community values.

“You have to wait for a diagnosis first”: Barriers to preventive mental health support and early interventions for children and young people in Sweden

by Karin Törnbom, Dominique Hange, Eva-Lisa Petersson, Irene Svenningsson

Background

Despite increasing attention to youth mental health, children and adolescents in Sweden experience fragmented, inequitable care with regional variation. Delays in diagnosis, limited preventive interventions, and poor inter-sectoral collaboration contribute to significant unmet needs. This study investigates system-level challenges and stakeholder perspectives on opportunities to enhance care pathways.

Methods

We conducted a qualitative study in the Västra Götaland region, Sweden. Fourteen purposively selected participants – including senior executives, healthcare professionals, and parents took part in semi-structured interviews. We used systematic text condensation, according to Malterud, and the four steps involved in this method for analysing the interviews.

Results

A central theme across interviews was the requirement for a formal diagnosis before children can access mental health support, particularly in school and primary care settings. Participants described this as a major barrier that delays early intervention and leaves children and young people with complex or atypical presentations without adequate support. Primary care professionals reported increasing mental health caseloads without corresponding increases in staffing or funding, limiting preventive work. Child and adolescent psychiatry (BUP) was described as overwhelmed, with long waiting times and limited continuity of care. A care manager within primary care was proposed as a way to help families navigate fragmented services and improve collaboration, although participants emphasised that such a role would need to be part of broader structural reform.

Conclusions

Our findings highlight persistent systemic issues in mental health care for children and young people, including inequitable access, insufficient prevention, and fragmented collaboration across sectors. Strengthening primary prevention, reallocating resources to primary and school-based mental health care and implementing well-defined care coordination roles within broader restructuring may improve continuity and equity in service delivery. Comprehensive policy reform is needed to support person-centred, integrated care pathways for children and young people with mental health needs.

Prediction of pre- and postfusion conformations of class I fusion proteins with AlphaFold2

by Sevilay Gülesen, Victoria Most, Clara T. Schoeder, Jens Meiler

Viruses such as coronaviruses or filoviruses use their surface glycoproteins (GPs) to attach to the host cell, triggering the fusion of the viral membrane with the endosome membrane. Epitopes on the viral GP are major targets for antibody-mediated recognition and neutralization. During the fusion process, the GP undergoes conformational changes triggered by fluctuations in environmental pH. Structural states are typically classified into three distinct conformations: prefusion, intermediate, and postfusion. These conformations serve as essential templates for prediction of conformational epitopes and structure-based vaccine design. Despite their importance, many viral GP structures remain absent from the Protein Data Bank (PDB). Fortunately, recent breakthroughs in computational structure prediction have greatly enhanced the accuracy and accessibility of protein modeling. In this study, we utilized AlphaFold2-Multimer (AF2-M), version 2.3, to predict various GP structural conformations and observed that the overall frequency of predictions in the postfusion conformation is low. Therefore, we hypothesized that adapting the AF2-M protocol is necessary to enrich for specific conformations, thereby enabling the prediction of both pre- and postfusion conformations. AF2-M requires only the input sequence and internally generates multiple sequence alignments (MSAs) and optional templates before applying its pretrained model weights. We tested the use of template data to enrich pre- or postfusion conformations and demonstrated that our approach significantly increases the prediction frequency of class I fusion protein structures in both conformations, with the template dataset playing a crucial role in guiding modeling towards the intended state. Furthermore, we showed that the lack of correlation between pLDDT and TM-scores suggests that low pLDDT values may obscure the presence of valid alternative conformations.

The evolution of life size Barbie and Ken: Are they any closer to reality?

by Sara Grafenauer, Belinda Durey, Kevin Norton

Barbie and Ken dolls have been criticized over time for their overt misalignment of body shape in comparison with the average adult, and the possibility that this impacts the formative minds of children, particularly girls. Updating a previous examination of the original Barbie and Ken dolls from 1996, this study compared the body measures of the 2016 “Fashionista” range—including Curvy, Petite, Tall, and Standard Barbie models, and new Malibu Ken—with representative population data of young adult females and males using anthropometric techniques. A range of anthropometric girth measures plus height were taken from each doll, and body proportions were calculated. The rules of allometry were used to scale the dolls to a standardized adult height of 170.18 cm to determine the dimensions the dolls at this adjusted size. The dimensions were then compared to the same height-adjusted reference population norms used in the original study. The comparison revealed significant alterations in the dolls’ morphology compared with the original Barbie and Ken, with key measures of waist-to-hip and chest-to-waist ratios becoming more realistic and falling within the 95% confidence range of the population. According to z-score deviation data, Curvy Barbie fell closest to the mean for most of the scaled girth measures, while new Ken was closer to the mean for all girths except ankle. Design changes reflect a shift toward greater body diversity, with potential benefits for children’s health behaviours through the production of a broader range of more diverse, human-like dolls. Importantly, key measurements and body proportions were generally closer to the respective reference populations.

Persistent symptoms, cognitive impairment, and clinical predictors of long COVID one year after Omicron infection: A clinical case–control study from the Faroe Islands

by Gunnhild Helmsdal, Marnar Fríðheim Kristiansen, Eyðbjørg Klemmentsen Gaard, Barbara Joensen Eysturoy, Pál Weihe, Eina Hansen Eliasen, Maria Skaalum Petersen

Background

Six years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.

Objectives

The aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.

Methods

We conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).

Results

A total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13–1.30, p  Conclusions

One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.

The role of attachment type and bone height in modulating stress distribution in mandibular overdentures: Insights from finite element analysis

by Burç İhsan Gencel, Melahat Çelik Güven, Uğur Mercan, Süleyman Çağatay Dayan, Onur Geçkili

Background

Mandibular two-implant overdentures are considered the standard of care for edentulous patients. The attachment system and the shape of the bone crest can significantly influence biomechanical behaviours. This study aimed to evaluate stress distribution in mandibular implant-supported overdentures using locator and bar attachments across various bone crest designs.

Materials and methods

FEA was performed on mandibular overdentures supported by two implants. Three crest configurations (flat, convex, and irregular) were modelled with either bar or locator attachments. A vertical force of 100 N was applied in three loading conditions: anterior, unilateral molar, and bilateral molar. Maximum von Mises stresses and principal stresses were assessed.

Results

Anterior loading resulted in the highest stresses across all groups, with peak values reaching 12 N/mm² in the convex and irregular models. Bilateral molar loading consistently produced the lowest and most uniform stress distributions, while unilateral loading caused intermediate stress concentrations on the working side. Uneven platforms significantly increased stress levels, particularly under unilateral bar loading. Locator attachments showed slightly reduced stresses after bilateral loading in irregular crest configurations. Stress concentrations were primarily localized at the implant neck and prosthetic connectors.

Conclusion

Stress distribution in mandibular overdentures is significantly influenced by loading direction, crest shape, and attachment mechanism. Anterior loading poses the highest biomechanical risk, while bilateral posterior loading provides optimal conditions. Vertical discrepancies in implant platforms heighten stress concentrations, underscoring the importance of careful surgical planning. Locator attachments offer limited biomechanical advantages in uneven crest scenarios, supporting their use in anatomically challenging cases.

Association between increased duodenal eosinophil count and functional dyspepsia

by Imteaz Mahbub, Bimal Chandra Shil, Sadeed Araf Reza

Background

Functional dyspepsia (FD) is a common gastrointestinal disorder with multifactorial pathogenesis. Recent evidence suggests that duodenal eosinophilia may contribute to low-grade immune activation in FD. This study evaluated the association between increased duodenal eosinophil count and functional dyspepsia.

Materials and methods

This case-control study was conducted in the Department of Gastroenterology, Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh, from January to December 2022. Forty-six adult patients with functional dyspepsia diagnosed by Rome-III criteria were included as cases, while forty age- and sex-matched individuals without functional dyspepsia undergoing upper gastrointestinal endoscopy for other indications with normal endoscopic findings served as controls. Multiple biopsies were obtained from the second part of the duodenum. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin and eosin. Eosinophils were counted manually by light microscopy in five randomly selected high- power fields (x 400 magnification), and the mean eosinophil count per high-power field (HPF) was calculated.

Results

The mean duodenal eosinophil count was significantly higher in patients with functional dyspepsia compared with controls (23.98 ± 7.98 versus 15.63 ± 5.94 eosinophils/HPF, p Conclusions

Patients with functional dyspepsia demonstrated significantly greater duodenal eosinophil infiltration than controls, supporting the role of low-grade immune activation in its pathogenesis. Further multicenter studies with larger samples are required to clarify the clinical implications of duodenal eosinophilia in functional dyspepsia.

Association between menstrual-related disorders and sexually transmitted infections: A nationwide cross-sectional study in Japan

by Tatsuya Yoshihara, So Owada, Harumasa Arita, Akiko Nakagomi, Kota Tanaka, Yosuke Ono, Osamu Yoshino

Background

To investigate the association between menstrual-related disorders and sexually transmitted infections (STI) among young women in Japan, and to examine differences according to disorder type and hormonal therapy use.

Methods

This cross-sectional study used the Japan Medical Data Center Claims Database and included women younger than 40 years who had at least one healthcare visit in 2023. Menstrual-related disorders were defined as endometriosis or dysmenorrhea based on ICD-10 codes. The prevalence of five STIs—gonorrhea, genital chlamydia infection, trichomoniasis, genital herpes, and other sexually transmitted conditions—was compared between women with and without menstrual-related disorders. Subgroup analyses were conducted for endometriosis, dysmenorrhea, and hormonal therapy (low-dose estrogen–progestin combinations or dienogest). Prevalence ratios (PR) and prevalence differences (PD) with 95% confidence intervals (CI) were estimated.

Results

Among 3,440,929 women, 257,897 (7.5%) had menstrual-related disorders. All STI were substantially more prevalent in this group than in women without menstrual-related disorders, with PRs ranging from 4.31 to 5.29. Endometriosis showed the highest prevalence, particularly for genital chlamydia infection (4.98%; PR 7.44). Dysmenorrhea was also associated with consistently elevated STI prevalence. Among women with menstrual-related disorders, STI prevalence differed only slightly according to hormonal therapy use, with differences generally within one percentage point.

Conclusion

Menstrual-related disorders were strongly associated with increased diagnosis of STI in Japanese young women. These findings highlight the importance of integrating STI screening and reproductive health education into routine gynecologic care for women with endometriosis or dysmenorrhea. The influence of healthcare-seeking behavior and diagnostic patterns should be considered when interpreting claims-based STI data.

Calcitonin as an adjunct for phantom limb pain

by Sneha Vidyasagar, Kanakamani Jeyaraman, Syeda Farah Zahir, Paul Varghese

Objective

This retrospective study evaluated calcitonin as an adjunct therapy for reducing phantom limb pain (PLP) following lower limb amputation.

Method

The study included 35 patients who received at least 3 days of calcitonin treatment between January 1, 2017, and December 31, 2023. We collected demographic data and pain ratings (intensity, distress, and interference with activity) before and after calcitonin treatment. Descriptive statistics and paired t-tests analysed the data, with a two-way repeated measures ANOVA used to compare outcomes between patients with and without diabetes. Raw and Standardized mean differences (Cohen’s d) are presented for each measure.

Results

The average age of participants was 57.09 years (SD = 13.66), with 40% female. Amputation types were below-knee (65.7%), above-knee (25.7%), and other (8.6%). The main causes of amputation included diabetic foot infection (25.7%), peripheral vascular disease (34.3%), trauma (25.7%), and other (14.3%). Ten participants had diabetes, and 20% had depression.Calcitonin was associated with significant reductions in pain outcomes from pre- to post-intervention (Day 0 to Day 7), with calcitonin given from day 1–3. Mean pain intensity decreased from 6.41 to 5.24 (Cohen’s d = 0.66); p = 0.02), and pain-related distress decreased from 5.85 to 4.81 (Cohen’s d = 0.71; p = 0.014). Perceived pain relief scores increased from 33.69 to 58.21, indicating greater patient-reported pain relief following treatment (Cohen’s d = 0.53; p = 0.035). No significant differences in pain intensity or distress were observed between patients with and without diabetes. Additionally, there was no significant change in the Oral Morphine Equivalent Daily Dose (p = 0.94).

Conclusion

In conclusion, calcitonin significantly reduced perceived pain intensity and pain-related distress scores while increasing perceived pain relief scores (i.e., patients’ reported degree of pain reduction), with similar effects observed in both patients with and without diabetes.

<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.

Tuberculosis death prediction calculator for prospective use at diagnosis in resource-constrained programme settings: a statewide cohort study

Por: Shanmugasundaram · S. · Shewade · H. D. · Srinivasan · R. · Frederick · A. · Sabarinathan · R. · Harish · P. · Balu · D. · Melfha · J. M. · Gayathri · K. · Vijayaprabha · R. · Jeyakumar · A. · Kabir · D. · Eraivan · M. · Bhatnagar · T. · Murhekar · M. V.
Objectives

To develop predictive models for early and overall tuberculosis (TB) deaths for prospective use at TB diagnosis in resource-constrained TB programme settings.

Design

Statewide cohort study using routinely captured secondary data.

Setting

With the majority of TB deaths being early (within 2 months), India’s TB programme’s information management system (Ni-kshay)-dependent death prediction models (using age, gender, TB site, previous treatment, microbiological confirmation, HIV, diabetes and bank account availability) are not feasible for prospective use, as few variables are captured at diagnosis. Utilising routinely captured triage variables for severe illness at diagnosis (body mass index, pedal oedema, respiratory rate, oxygen saturation and ability to stand without support) from an ongoing statewide and state-specific differentiated TB care initiative to reduce TB deaths in Tamil Nadu state (southern India, 80 million population with 0.1 million annual notifications), robust models for prospective use were developed.

Participants

Adults (aged ≥15 years) with TB (not known to be drug-resistant at diagnosis) that were notified from public facilities of Tamil Nadu from July 2022 to June 2023.

Outcome measures

Early and overall (within 12 months of notification) TB deaths. Area under the receiver operating characteristic curve (AUC) was used to assess accuracy of models built using modified Poisson regression.

Results

Among 55 971 adults, the overall death rate was 7.4%, and 67.9% of the deaths were early. In predicting overall deaths, accuracy of the model using all Ni-kshay variables (AUC 0.716 (95% CI 0.707 to 0.725)) was as good as the model using triage variables for severe illness only (AUC 0.701 (95% CI 0.691 to 0.711)). To the latter, adding potentially capturable Ni-kshay variables at diagnosis (age, gender, TB site, previous treatment and microbiological confirmation) significantly improved model accuracy (AUC 0.754 (95% CI 0.745 to 0.763)). Further addition of remaining Ni-kshay variables did not improve accuracy significantly. Death prediction equations were generated for these models.

Conclusion

Simple and easily measurable triage variables for severe illness should be routinely captured at TB diagnosis. A death prediction calculator (http://44.208.93.99/) based on these variables (specifically triage variables for severe illness combined with age, gender, TB site, previous treatment and microbiological confirmation) may be used by Indian states and high TB burden countries seeking scalable, data-driven interventions to reduce TB deaths.

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