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Genetic ablation of interleukin-17A augments fibrosis in a mouse model of cholestatic liver injury

by Takashi Kitagataya, Anuradha Krishnan, Kirsta E. Olson, Florencia Gutierrez, Michelle Baez-Faria, Maria Eugenia Guicciardi, Kevin D. Pavelko, Adiba I. Azad, Gregory J. Gores

Aim

The underlying mechanisms contributing to cholestatic liver injury remain unclear. The pro-inflammatory leukocyte-restricted cytokine interleukin-17A (IL-17A) has been implicated in human cholestatic liver injury. However, mechanistic insights are lacking and require further exploration in preclinical models. Herein, we examined the effect of IL-17A genetic ablation in a mouse model of cholestatic liver injury.

Method

Age and gender-matched littermate wild type (WT) and Il-17a-/- C57BL/6 mice were fed an intermittent 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 21 days to induce cholestatic liver injury or a control diet.

Results

As compared to WT littermates, Il-17a-/- mice displayed more abundant desmin-positive myofibroblasts and increased fibrosis. NanoString analysis of intrahepatic leukocyte populations using a fibrosis-related gene panel identified upregulation of Tnfsf14 (encoding the protein LIGHT) in the DDC-fed Il-17a-/- mice. Although mass cytometry identified an increase in myeloid cells in both genotypes of the DDC-fed mice, we could not identify LIGHT expression in this cell lineage. Instead, the upregulation of LIGHT expression was largely restricted to a CD4+ T cell population as assessed by flow cytometry. Enhanced LIGHT expression was observed in a Th1+ CD4+ T cell population. LIGHT activated primary human hepatic stellate cells in vitro, suggesting that LIGHT stimulation of hepatic fibrogenesis may be direct.

Conclusion

Taken together, these data suggest that IL-17A restrains expression of the profibrogenic cytokine, LIGHT, by Th1-polarized CD4+ T cells, and implicate a role for LIGHT in cholestatic fibrogenesis in DDC-fed mice; a finding which requires validation in additional models.

Study protocols for the GEPard project: systematic analysis of sex- and gender-specific differences in the efficacy of perioperative pain management - a two-pronged approach

Por: Floren · S. · Segelcke · D. · Machacek · P. A. · Vollert · J. · Norda · H. · Rohde · I. · Gilron · I. · Pogatzki-Zahn · E. M.
Introduction

Postoperative pain is common, with approximately one-third of surgical patients experiencing severe acute pain and 10–20% developing chronic post-surgical pain (CPSP). Evidence shows that female patients are at higher risk of pain after sex non-specific surgery, thus sex- or gender-specific differences in pain treatment efficacy with potential consequences for perioperative pain management are to be expected. Considering the clinical and societal burden of poorly managed postoperative pain, the GEPard project comprises two systematic reviews, GEPard 1: sex- and/or gender-specific differences in efficacy of perioperative pain management for certain (major) surgical procedures in adult patients; and GEPard 2: sex- and/or gender-specific differences in the dosing, efficacy and adverse effects of the most common systemic perioperative non-opioid- and co-analgesics across all sex non-specific surgical procedures in adult patients.

Methods and analysis

The reviews will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook. MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov and PsycINFO will be searched. We will include randomised controlled trials (RCTs) and systematic reviews/meta-analyses reporting outcomes disaggregated by sex and/or gender in adult surgical patients. For GEPard 1, this applies to selected major surgical procedures; for GEPard 2, to all non-sex-specific surgical procedures. Interventions include regional anaesthesia, systemic analgesics and psychological strategies for GEPard 1 and non-opioid- as well as co-analgesics for GEPard 2. Two reviewers will independently screen and extract the data. Cochrane Risk of Bias Tool 2.0 (RoB 2) and AMSTAR 2 tools will assess study quality. Random-effects or Bayesian meta-analyses will be performed where possible; otherwise, narrative synthesis will be applied. GRADE methodology will assess evidence certainty.

Ethics and dissemination

No ethical approval is required for these reviews. Findings will be disseminated via peer-reviewed publications, patient organisations and professional societies. Data will be shared via Zenodo or Open Science Framework (OSF), following FAIR principles.

PROSPERO registration number

The systematic review protocols for both reviews have been registered in PROSPERO on 29 August 2025 (Registration-ID: CRD420251121393 (GEPard1), CRD420251121536 (GEPard2).

Systematic Reviews of Psychosocial Interventions for Loneliness Among Older Adults in Community and Residential Care Settings: An Umbrella Review

ABSTRACT

Aim

To describe the latest information on types of psychosocial interventions and their effectiveness on loneliness reduction among older adults in community and residential care settings, and the experience with these interventions.

Design

Umbrella review.

Methods

The Joanna Briggs Institute methodology for umbrella reviews.

Data Sources

Cochrane Database of Systematic Reviews; Cumulative Index of Nursing and Allied Health Literature; Medline; Embase; Emcare; PsycINFO; ProQuest Dissertation & Thesis Global; Ovid Nursing Database; MedRxvi.

Results

Twenty-two reviews were included. Seven major types of psychosocial intervention were identified: (1) social facilitation interventions, (2) psychological therapies, (3) health and social care provision, (4) animal-assisted interventions, (5) befriending interventions, (6) leisure and skill development, and (7) other interventions. Social facilitation interventions that provide synchronised interaction, psychological therapies, health and social care provision, and animal (−assisted) interventions demonstrated positive effects while leisure/skill development and befriending interventions warrant more rigorous evidence. Group settings, synchronised interaction and purpose-driven are identified as facilitators, whereas technological issues and safety issues are barriers to participation.

Conclusion

Seven types of psychosocial interventions are currently available for loneliness among community-dwelling older adults, and a positive effect in reducing loneliness was demonstrated in some types. Facilitators and barriers to their participation were synthesised. Two future research directions are suggested: (1) reviews on meaning-centred interventions to provide a comprehensive understanding and (2) implementation studies employing community-based paraprofessionals to promote programme scalability and accessibility.

Implications for the Profession

Health and social care practitioners (e.g., nurses), researchers and policymakers are recommended to employ social facilitation interventions with synchronised interaction, psychological therapies, health and social care provision and animal-assisted interventions to address loneliness among community-dwelling older adults.

Impact

This review provided empirical information on available effective interventions to address loneliness among community-dwelling older adults. It also provided information for nurses to implement psychosocial interventions in the community.

Reporting Method

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines

Patient or Public Contribution

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

Trial Registration

PROSPERO CRD 42023482852, registered 25/11/2023

Self-management measurement instruments specific to individuals with cardiovascular diseases: a systematic review protocol using COSMIN methodology

Introduction

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, making the development of self-management strategies crucial for preventing complications and improving clinical outcomes. This process involves symptom monitoring, treatment adherence, emotional management and a healthy lifestyle, among others. Reliable instruments are necessary to measure self-management, requiring robust psychometric properties. In this way, this COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)-based systematic review aims to assess the quality of specific self-management instruments for adults with CVDs.

Methods and analysis

This systematic review will follow the COSMIN and be reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol. Searches will be conducted in seven databases: MEDLINE, Web of Science, Scopus, PsycINFO, EMBASE and CINAHL. Additionally, a manual search will be performed on PROQOLID, PROMIS and The Medical Outcome Trust websites. Studies on the development and validation of patient-reported instruments measuring specific self-management for individuals with CVDs will be included, without language or date restrictions. The search will be performed in November 2025, with the final version of the review expected to be completed in October 2026. Data extraction will follow COSMIN recommendations. The Modified Grading of Recommendations, Assessment, Development and Evaluation approach will be used to determine the quality of evidence. Instruments will be categorised according to COSMIN recommendations. All steps will be conducted by two independent reviewers, with a third reviewer involved in case of discrepancies. Additionally, the content of the instruments will be analysed and linked to the International Classification of Functioning, Disability and Health, following international recommendations.

Ethics and dissemination

This study does not require ethics committee approval as it is a review of published data. The review results will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

PROSPERO registration number

CRD42024605969.

Evaluation of a commercial pressure cooker for the preparation of agar media for a diagnostic microbiology laboratory

by Joseph E. Rubin, Florence Huby, Roshan P. Madalagama, Shyamali de Alwis, Melinda Wyshynski, Rasika Jinadasa

The ability to prepare sterilized media is a critical capability of any microbiology lab. Diagnostic labs in low-resource settings, which lack autoclave facilities, are therefore severely limited in their ability to perform basic assays such as bacterial culture or biochemical tests. This investigation aimed to validate the use of a commercially available pressure cooker as an autoclave substitute to produce agar plates. First, a Geobacillus stearothermophilus biological indicator was used to confirm adequate sterilization. Next, the colony morphology of several important bacterial species were compared on MacConkey and 5% sheep’s blood agar plates prepared using the pressure cooker with those made in an autoclave. Finally, disc diffusion susceptibility testing was performed to determine whether the sterilization method impacts the inhibitory zone diameters. Overall, the morphology of colonies was similar on media prepared in both ways; key phenotypic characteristics (lactose fermentation, colour, shape, hemolysis and smell) were the same. Kirby-Bauer disc diffusion test results were nearly identical. These findings indicate that a commercially available pressure cooker may be suitable to prepare media in low-resource laboratories.

Nursing Care in Hospital Settings for Victims of Mental Disorders: Systematic Review With Meta‐Aggregation

ABSTRACT

Introduction

Approximately 25% of the Brazilian population suffers from mental disorders, a prevalence exacerbated by systemic and cultural factors such as socioeconomic inequalities, underfunded mental health services, regional disparities, and persistent stigma. These conditions significantly impact hospital care. Nurses, due to their direct contact with these patients, face challenges ranging from managing physical conditions to handling verbal aggression and psychiatric crises. This study aimed to assess the scientific evidence regarding nursing care for hospitalized patients with psychiatric disorders.

Methods

A systematic review with a mixed-methods approach was conducted, registered in PROSPERO (#CRD42022359288) and guided by PRISMA standards. Databases, such as MEDLINE, LILACS, PubMed, Web of Science, Scopus, and BDEnf, were searched using keywords like “Mental disorder,” “Psychiatric health,” “Nursing care,” and “Hospital.” Methodological quality was assessed using JBI and SQUIRE tools. The integration of quantitative and qualitative components occurred through meta-aggregation of qualitative data and frequency-based coding of quantitative themes, allowing thematic convergence across study designs.

Results

Six studies were included. Meta-aggregation revealed frequent terms, such as “Nurse,” “Emergency,” “Screening,” “Patient,” and “Care.” Similarity analysis linked “Nurse” with “perception” and “experience” and “Emergency” with “Screening” and “Mental health,” highlighting the importance of experience and training. Five categories emerged: (1) professional experience (19.05%, showing skill gaps despite experience); (2) caring process (19.05%, stressing efficient screening); (3) barriers and challenges (19.05%, revealing difficulty with comorbidities); (4) training process (19.05%, identifying training deficiencies); and (5) therapeutic interventions (23.81%, discussing restraint use). These percentages refer to the proportional frequency of themes identified across the total number of studies analyzed. For thematic classification, only statistically significant chi-square values (p < 0.05) were considered in the grouping of content.

Conclusion

Nursing care for psychiatric patients in hospitals faces challenges like insufficient training and difficulty managing psychiatric comorbidities. Recommendations include incorporating structured mental health content into nursing curricula and hospital-based continuing education programs. These strategies may guide future healthcare policies in Brazil by improving patient safety, reducing hospital readmissions, and promoting more humane, evidence-based therapeutic interventions.

Clinical Relevance

The findings emphasize the urgent need for targeted education and training to improve nursing care for psychiatric patients in hospital settings.

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