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Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

A comparative vignette study: Evaluating the potential role of a generative AI model in enhancing clinical decision‐making in nursing

Abstract

Aim

This study explores the potential of a generative artificial intelligence tool (ChatGPT) as clinical support for nurses. Specifically, we aim to assess whether ChatGPT can demonstrate clinical decision-making equivalent to that of expert nurses and novice nursing students. This will be evaluated by comparing ChatGPT responses to clinical scenarios to those of nurses on different levels of experience.

Design

This is a cross-sectional study.

Methods

Emergency room registered nurses (i.e. experts; n = 30) and nursing students (i.e. novices; n = 38) were recruited during March–April 2023. Clinical decision-making was measured using three validated clinical scenarios involving an initial assessment and reevaluation. Clinical decision-making aspects assessed were the accuracy of initial assessments, the appropriateness of recommended tests and resource use and the capacity to reevaluate decisions. Performance was also compared by timing response generations and word counts. Expert nurses and novice students completed online questionnaires (via Qualtrics), while ChatGPT responses were obtained from OpenAI.

Results

Concerning aspects of clinical decision-making and compared to novices and experts: (1) ChatGPT exhibited indecisiveness in initial assessments; (2) ChatGPT tended to suggest unnecessary diagnostic tests; (3) When new information required re-evaluation, ChatGPT responses demonstrated inaccurate understanding and inappropriate modifications. In terms of performance, the mean number of words utilized in ChatGPT answers was 27–41 times greater than that utilized by both experts and novices; and responses were provided approximately 4 times faster than those of novices and twice faster than expert nurses. ChatGPT responses maintained logical structure and clarity.

Conclusions

A generative AI tool demonstrated indecisiveness and a tendency towards over-triage compared to human clinicians.

Impact

The study shows that it is important to approach the implementation of ChatGPT as a nurse's digital assistant with caution. More study is needed to optimize the model's training and algorithms to provide accurate healthcare support that aids clinical decision-making.

Reporting method

This study adhered to relevant EQUATOR guidelines for reporting observational studies.

Patient or public contribution

Patients were not directly involved in the conduct of this study.

Hospitals financial performance across European countries: a scoping review protocol

Por: Dubas-Jakobczyk · K. · Ndayishimiye · C. · Szetela · P. · Sowada · C.
Introduction

Hospitals remain the cornerstone of health systems in European countries. Therefore, the financial sustainability of hospitals constitutes an important determinant of healthcare provision security. The fragmentary data available indicate that hospitals in many European countries are continuously facing financial deficits and/or insolvency problems. Yet a comparative analysis of hospital financial performance across European countries has been lacking. The proposed review will, therefore, fill in an important research gap and build a knowledge base on the topic of assessing and monitoring the financial sustainability of hospitals in Europe. The general objective is to identify, synthetise and map existing evidence on hospital financial performance across European countries.

Methods and analysis

This scoping review will follow six stages: (1) defining the research question, (2) identifying relevant literature, (3) studies selection, (4) data extraction, (5) collating, summarising and reporting of results and (6) consultation process and involvement of knowledge users. The following databases will be searched:(1) Medline via PubMed, (2) Web of Science Core Collection, (3) Scopus and (4) ProQuest Central. In addition, a Google Engine search will also be performed. Furthermore, reference lists of relevant papers will be visually scanned to identify further studies of interest. The review will include both quantitative and qualitative empirical studies as well as theoretical papers and technical reports. The PRISMA extension for a Scoping Review checklist will be used for reporting.

Ethics and dissemination

Formal ethical approval is not required because no primary data will be collected in this study. Results will be published in a peer-reviewed journal. The findings will also be disseminated through conference presentations and summaries to key stakeholders.

Molecular characterization of chronic cutaneous wounds reveals subregion‐ and wound type‐specific differential gene expression

Abstract

A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.

U.S. nursing home leadership experiences with COVID-19 and its impact on residents and staff: A qualitative analysis

by Catherine E. Dubé, Natalia Nielsen, Emily McPhillips, J. Lee Hargraves, Carol Cosenza, Bill Jesdale, Kate L. Lapane

Objectives

To explore experiences of U.S. (United States) nursing home leadership during the COVID-19 pandemic in their efforts to address resident loneliness and social isolation and to elicit stories about personal and professional impacts on themselves and staff.

Design

Qualitative inquiry via three optional open-ended questions appended to a national self-administered survey of American nursing home leaders was employed. Textual data was analyzed using an iterative reflexive thematic approach.

Setting and participants

A stratified sample frame defined by facility size (beds: 30–99, 100+) and quality ratings (1, 2–4, 5) was employed. Web survey links and paper surveys were sent to 1,676 nursing home directors of nursing between February and May 2022.

Results

Open text responses were collected from 271 nursing homes. Broad themes included: 1) Addressing needs of residents & families; 2) Challenges; and 3) Personal experiences of nursing home leadership/staff. Respondents described trauma to residents, staff, and leadership. Resident loneliness was addressed using existing and newer technologies and innovative indoor and outdoor activities. Residents experienced fear, illness, loss, and sometimes death. Isolation from family and lack of touch were particularly difficult. Regulations were seen as punitive while ignoring emotional needs of residents. Staffing challenges and pressures to do more with less created additional stress. Leadership and staff made significant sacrifices resulting in physical, social, and emotional consequences. Beneficial outcomes included staff bonding, professional growth, and permanent implementation of new interventions.

Conclusions and implications

New and creative interventions were successfully implemented to address social isolation and loneliness. Improved Wi-Fi and other nursing home infrastructure upgrades are needed to maintain them. Reimagining often conflicting overlapping federal, state, and local regulations, grounding them in good clinical judgement, and incentivizing performance improvement should be considered. Trauma experienced by staff needs to be addressed to deal with current and future workforce needs.

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