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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.

Impact of chronic oral glucocorticoid treatment on mortality in patients with COVID-19: analysis of a population-based cohort

Por: Einarsdottir · M. J. · Kibiwott Kirui · B. · Li · H. · Olsson · D. · Johannsson · G. · Nyberg · F. · Ragnarsson · O.
Objectives

While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes.

Design

Population-based observational cohort study.

Settings

Population-based register data in Sweden.

Participants

All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153).

Outcome measures

Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses.

Results

3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction.

Conclusion

Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.

Actualization of evidence‐based nursing in primary, specialized, and social care settings—A cross‐sectional survey

Abstract

Background

Basing practice on evidence is a widely acknowledged requirement for nursing, but shortcomings still exist. An increased understanding of the actualization of evidence-based nursing (EBN) across different nursing contexts is needed to develop better support for EBN and promote uniform high-quality nursing.

Aims

The aim of this study was to compare the actualization of EBN in different organizational contexts in Finland.

Methods

Data for this survey were collected in 2021. The actualization of EBN in primary, specialized, and social care organizations was evaluated with the Actualization of Evidence-Based Nursing instrument, nurses' version, which focuses on individual and organizational-level EBN support structures. Differences between (1) specialized and primary healthcare, and (2) different nursing practice settings were tested with Welch's two sample t-test, the Kruskal–Wallis rank sum test, and the Wilcoxon rank sum test.

Results

Based on nurse (n = 1020) evaluations, those working in specialized healthcare hold more positive attitudes toward EBN (p = .021) and evaluated their organization's methods for monitoring and evaluating nursing practices (p = .004) more positively than those working in primary healthcare. Regarding different nursing practice settings (n = 1241), the most positive results were observed within preventive healthcare where nurses evaluated their attitudes toward EBN, EBN competence, and personal evidence-based practices more positively compared to other nursing practice settings. The results were parallel regarding several organizational structures for EBN. Positive results were also observed within somatic units at university hospitals, and most negative results were within institutional care settings, health centers, and home care settings.

Linking Evidence to Action

There is a need for targeted support to strengthen EBN across different organizational contexts, with special attention to those contexts where nursing professionals with lower education levels work. Future research needs to focus on further analyzing the organizational differences and what can be learned, especially from preventive healthcare but also somatic units at university hospitals.

The relationship between sensory impairment and home care client's received care time—A cross‐sectional study

Abstract

Aim

The aim of this study was to explore the relationship between sensory impairment and home care client's received care time.

Design

A cross-sectional multi-source study.

Methods

Data from a self-reported staff survey on care time allocation were merged with registry data from the Resident Assessment Instrument registry (n = 1477). The data were collected during 1 week from 17 home care units in Finland in October 2021. The relationship between sensory impairment and clients received care time was examined using linear regression analyses.

Results

The linear regression analyses showed that having vision impairment alone increased care time, while dual sensory impairment resulted in decreased received care time. Hearing impairment alone was not statistically significantly associated with care time.

Conclusion

The holistic care need of home care clients with dual sensory impairment may not be adequate. To ensure equality and the individually tailored care of clients, further attention must be paid to clients with sensory impairments, especially those with dual sensory impairment. Furthermore, the competence of home care workers to encounter and communicate with clients with sensory impairment must be developed to support the holistic care.

Implications for the patient care

The sensory impairments of home care clients must be identified in time and considered in care planning and encountering clients.

Impact

As there is a risk that clients with dual sensory impairment are not able to fully express themselves, it is imperative that further attention is paid to clients with sensory impairments, to better understand and support this vulnerable group. Increased awareness and continuous education are needed to better identify and support home care clients with sensory impairment.

Reporting Method

The study adheres to the STROBE reporting guidelines.

Patient or public contribution

No patient or public contribution.

The significance of parental mentalizing for four-year-old children’s solitary pretend play

by Johanne Smith-Nielsen, Anne Christine Stuart, Katrine Isabella Wendelboe, Ida Egmose, Camilla Overbye Roos, Mette Skovgaard Væver

Background

Pretend play is a signature behavior of early childhood and is considered to reflect the child’s emerging symbolic function, enabling the interpretation of social signals, language development, and emotion understanding. While theory links parental mentalizing with children’s pretend play, only a few studies have investigated this association. These studies are limited to infancy and early toddlerhood, and child pretend play is assessed during play with an adult (social play). Based on the assumption that child solitary pretend play reflects the child’s ‘baseline’ pretend play ability, in this study, we investigated children’s pretend play at its peak, i.e., during the preschool age, without the facilitation of another player. The overall objective was to investigate if parental mentalizing increases pretend play complexity in children.

Methods

The sample consisted 99 Danish mothers and their 4-year-old children. Employing a cross-sectional design, we hypothesized that parental mental state language, as an indicator of ‘online’ mentalizing during interaction with the child, is a mechanism through which ‘offline’ mentalizing, measured as parental reflective functioning, is associated with child solitary pretend play. Child pretend play complexity was observed and coded with an adapted version of the 12-Step Play Scale. Maternal offline mentalizing was assessed with the Parental Reflective Functioning Questionnaire, and maternal online mentalizing was assessed by coding the mothers’ mental state language during interaction with the child using a modified version of the mind-mindedness coding scheme.

Results

While there was no direct effect of maternal offline reflective functioning on child pretend play, online mental state language mediated the link between offline maternal reflective functioning and child pretend play.

Conclusions

These results provide support for the theoretically assumed link between parental mentalizing and children’s capacity for pretend play. Furthermore, our study contributes to the literature on parental mentalization, suggesting that parental mentalizing facilitates child development only if the parent can translate this ability into ’mentalizing in action’.

The impact of cineole treatment timing on common cold duration and symptoms: Non-randomized exploratory clinical trial

by Andreas Michalsen, Kim Goldenstein, Peter Kardos, Ludger Klimek, Jürgen Palm, Dajana Parganlija, Johannes Stöckl

Introduction

Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset.

Methods

Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11).

Results

Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p Conclusions

Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.

Nurses' and physicians' perspectives on implementation barriers and facilitators in a transfer program for parents of adolescents with chronic illness

Abstract

Aim

To identify barriers and facilitators impacting the implementation of a comprehensive transfer program aimed at parents of adolescents with chronic illness in clinical practice.

Design

A real-time, qualitative process evaluation.

Methods

Individual interviews were conducted with 10 nurses and seven physicians from paediatric and adult outpatient clinics: Nephrology, hepatology, neurology, and rheumatology. Data were analysed through the lens of normalization process theory.

Results

Themes were framed within the theory's four components. (1) Coherence: Healthcare professionals' views on their core tasks and on the parents' role influenced their perception of the program. (2) Cognitive participation: A named key worker, autonomy, and collaboration impacted healthcare professionals' involvement in the program. (3) Collective action: Department prioritization and understanding of the program's aim were key factors in its successful delivery. (4) Reflective monitoring: Participants experienced that the program helped parents during transfer but questioned if the program was needed by all families.

Conclusion

We identified three barriers: Healthcare professionals' lack of understanding of the parental role during transfer, top-down decisions among nurses, and physicians' uncertainty about their role in joint consultations. Facilitators: Healthcare professionals' understanding of the program's purpose and expected effect, the nurses' significant role as named keyworkers, and good collaboration across paediatric and adult departments.

Implications for the Profession and/or Patient Care

Implementation strategies should be developed before implementing a transfer program in clinical practice.

Impact

Implementing a parental transfer program in clinical practice can be challenging. Therefore, for successful implementation, it is crucial to identify barriers and facilitators. Barriers and facilitators exist at the personal, professional, and organizational levels, and it is important to understand them. The results of this qualitative study could support the implementation of transfer programs in other settings.

Reporting Method

Consolidated criteria for reporting qualitative studies (COREQ).

Patient or Public Contribution

No patient or public contribution.

What does this paper contribute to the wider global clinical community?

Nurses' and physicians' experiences of ownership of the transfer program is essential for successful implementation. Clinics should appoint a named keyworker, preferably a nurse, as the driving force during the implementation of a transfer program. Nurses and physicians should receive training about the purpose, justification, and expected effect of a transfer program before implementation.

Experiences of improvement of everyday life following a rehabilitation programme for people with long‐term cognitive effects of COVID‐19: Qualitative study

Abstract

Aim and Objectives

To explore challenges in everyday life for people with long-term cognitive effects of COVID-19 and whether a rehabilitation programme contributed to the remedy thereof.

Background

Healthcare systems around the world need knowledge about acute COVID-19 treatment, long-term effects exerting an impact on peoples' everyday lives, and how to remedy these.

Design

This is a qualitative study with a phenomenological approach.

Methods

Twelve people with long-term cognitive effects of COVID-19 participated in a multidisciplinary rehabilitation programme. Individual semi-structured interviews were made. Data were analysed thematically.

Results

Three themes and eight sub-themes emerged with respect to everyday life challenges and experiences of the rehabilitation programme. The themes were (1) Personal insight and knowledge, (2) Changed daily routines at home and (3) Coping with working life.

Conclusion

Participants experienced long-term effects of COVID-19 as cognitive challenges, fatigue and headaches, which affected their everyday lives, that is inability to overcome daily tasks at home and at work, maintaining family roles and relations with relatives. The rehabilitation programme contributed to a vocabulary and insights related to the long-term effects of COVID-19 and the experience of being a different person. The programme contributed to changes in daily routines, organising breaks in everyday life and explaining challenges to family/relatives and the way in which they affected daily routines and their role in the family. In addition, the programme supported several of the participants in finding the right workload and working hours.

Relevance to Clinical Practice

We recommend multidisciplinary rehabilitation programmes inspired by cognitive remediation of long-term COVID-19 cognitive effects. Municipalities and organisations could collaborate in the development and completion of such programmes, possibly comprising both virtual and physical elements. This could facilitate access and reduce costs.

Patient or Public Contribution

Patients contributed to the conduct of the study by participating in the data collection via interviews.

Clinical Trial Registration Number

Data collection and processing of data are approved by the Region of Southern Denmark (journal number: 20/46585).

Systematic review of end stage renal disease in Pakistan: Identifying implementation research outcomes

by Hamad AlRashed, Johanna Miele, Joshua Prasad, Deborah Adenikinju, Chukwuemeka Iloegbu, John Patena, Dorice Vieira, Joyce Gyamfi, Emmanuel Peprah

Aim and objectives

The aim of this study was to conduct a systematic review analysis to identify and evaluate the available literature on implementation science outcomes research in relation to End Stage Renal Disease (ESRD) in Pakistan.

Methods

A systematic database search of PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and Ovid was conducted through October 22nd, 2022, without any restrictions on publication dates. A screening and data extraction tool, Covidence, was used to evaluate the literature against our inclusion and exclusion criteria. Furthermore, a Mixed Methods Appraisal Tool (MMAT) was used to evaluate the selected studies.

Results

We identified four studies that presented findings of implementation outcomes research which were related to appropriateness, feasibility, and acceptability. Appropriateness was examined using knowledge scores (p = 0.022) and medication adherence scores (p Conclusion

The preliminary results of this review indicate a gap in the availability of implementation research studies about ESRD in Pakistan. The burden of ESRD, and the implementation methods by which it is treated is notable in Pakistan and requires evidence-based measures to be implemented to support the critical healthcare delivery platforms that provide treatment.

Climate change-informed dietary modeling in Pacific cod: Experimentally-derived effects of temperature and dietary quality on carbon and nitrogen stable isotope trophic discrimination factors

by Matthew C. Rogers, Ron A. Heintz, Johanna J. Vollenweider, Ashwin Sreenivasan, Katharine B. Miller

Stable isotope analysis is a powerful tool for dietary modeling and trophic ecology research. A crucial piece of information for isotopic dietary modeling is the accurate estimation of trophic discrimination factors (TDFs), or the isotopic offset between a consumer’s tissue and its diet. In order to parameterize stable isotope dietary models for future climate scenarios, we investigated the effect of water temperature and dietary protein and lipid content on TDFs in juvenile Pacific cod (Gadus macrocephalus). Pacific cod are a commercially and ecologically important species, with stock numbers in the northeast Pacific recently having dropped by more than 70%. We tested four water temperatures (6, 8, 10, and 12°C) and two dietary regimens (low and high lipid content), representing a range of potential ocean temperature and prey quality scenarios, in order to determine carbon and nitrogen TDFs in juvenile Pacific cod. Additionally, we assessed dietary intake and proximate composition of the experimental fish in order to estimate consumption, assimilation, and retention of dietary nutrients. The results of this study suggest that dietary protein catabolism is a primary driver of nitrogen TDF variability in juvenile Pacific cod. Across all temperature treatments from 6 to 12°C, fish reared on the lower quality, lower lipid content diet had higher nitrogen TDFs. The mean TDFs for fish raised on the higher lipid, lower protein diet were +3.40 ‰ for nitrogen (Δ15N) and +0.36 ‰ for lipid-corrected carbon (Δ LC 13C). The mean TDFs for fish raised on the lower lipid, higher protein diet were +4.09 ‰ for nitrogen (Δ15N) and 0.00 ‰ for lipid-corrected carbon (Δ LC 13C). Lipid-corrected carbon isotope data showed that, regardless of temperature, fish consuming the lower lipid diet had essentially no trophic discrimination between diet and bulk tissues. We found no ecologically meaningful differences in TDFs due to water temperature across the 6°experimental range. The results of this experiment demonstrate that dietary quality, and more specifically the use of dietary protein for energetic needs, is a primary driver of trophic discrimination factors. The TDFs determined in this study can be applied to understanding trophic ecology in Pacific cod and closely related species under rapidly changing prey availability and ocean temperature conditions.

Polyethylene glycol precipitation is an efficient method to obtain extracellular vesicle-depleted fetal bovine serum

by Peng Wang, Onno J. Arntz, Johanna F. A. Husch, Van der Kraan P. M., Jeroen J. J. P. van den Beucken, Fons A. J. van de Loo

Mesenchymal stromal/stem cell derived-extracellular vesicles (MSC-EVs) have gained interest as drug delivery nanoparticles, having immunoregulatory and potentiating tissue repair property. To maintain growth of MSCs and obtain pure MSC-derived EVs, the culture media should contain fetal bovine serum (FBS) devoid of EVs, as the presence of FBS EVs confounds the properties of MSC-EVs. Therefore, we tested three methods: 18h ultracentrifugation (UC) and ultrafiltration (UF), which are common FBS EV depletion methods in current MSC-EV research, and polyethylene glycol (PEG) precipitation to obtain three EV depleted FBS (EVdFBS) batches, and compared them to FBS and commercial (Com) EVdFBS on human adipose stem cell (hADSC) growth, differentiation, enrichment of EVs in hADSC supernatant and their biological function on collagen metabolism. Our comparative study showed UC and UF vary in terms of depletion efficiency and do not completely deplete EVs and affects the growth-promoting quality of FBS. Specifically, FBS EV depletion was comparable between PEG (95.6%) and UF (96.6%) but less by UC (82%), as compared to FBS. FBS protein loss was markedly different among PEG (47%), UF (87%), and UC (51%), implying the ratio of EV depletion over protein loss was PEG (2.03), UF (1.11), and UC (1.61). A significant decrease of TGFβ/Smad signaling, involving in MSC growth and physiology, was observed by UF. After 96 hours of exposure to 5% FBS or 5% four different EVdFBS cell growth media, the osteogenesis ability of hADSCs was not impaired but slightly lower mRNA expression level of Col2a observed in EVdFBS media during chondrogenesis. In consistent with low confluency of hADSCs observed by optical microscope, cell proliferation in response to 5% UF EVdFBS media was inhibited significantly. Importantly, more and purer ADSCs EVs were obtained from ADSCs cultured in 5% PEG EVdFBS media, and they retained bioactive as they upregulated the expression of Col1a1, TIMP1 of human knee synovial fibroblast. Taken together, this study showed that PEG precipitation is the most efficient method to obtain EV depleted FBS for growth of MSCs, and to obtain MSC EVs with minimal FBS EV contamination.

Redefining sexual health after gynaecological cancer: Lived experiences from Gynea, a digital rehabilitation programme

Abstract

Background

Gynaecological cancer illness and treatment have a significant impact on women's sexual health and concerns regarding sexual health are known to be an unmet need in survivors. The digital support programme Gynea was designed to enhance women's health, including sexual health, after gynaecological cancer treatment. This study aimed to explore how cancer survivors experienced participation in Gynea.

Methodology

This is a phenomenological hermeneutic study. Individual, in-depth semi-structured interviews were conducted to explore lived experiences. Twenty women were interviewed after completing the Gynea programme. The transcripts were analysed using Lindseth and Norberg's phenomenological hermeneutic method.

Findings

Three main themes (with subthemes) emerged from the analysis: (1) A silent existential trauma; (2) Redefining sexual health; (3) Communicating with a partner about sexuality. The women redefined sexual health rather than just being sexual intercourse, being a rediscovery of the body. The women's increased awareness and understanding of their own sexual health empowered their communication about their sexuality with their partners. This was important for regaining sexual health and intimacy in their relationships.

Conclusion

Participation in Gynea helped to strengthen the women's sexual integrity. Knowledge and support empowered them to take care of their sexual needs and communicate these with their partners.

Implications for Patient Care

Healthcare services and nurses need to be aware that sexual health is an existential state of being, in which good sexual health does not necessarily equate to sexual function, but rather to sexual empowerment. Digital support with nurse guidance can support women in caring for their sexual health after cancer illness by thematizing sexual health with a holistic approach and should be part of the medical treatment.

Patient or Public Contribution

Twenty gynaecological cancer survivors contributed by sharing their experiences from the sexual health module in Gynea.

Supporting Parkinson's disease medication safety for nurses in the acute care setting through an educational intervention study

Abstract

Introduction

Patient medication safety in the acute care setting is a foundational action provided by nurses and healthcare providers for safe patient care. Hospitalization of patients with Parkinson's disease (PD) can be dangerous due to the unique and variable medication regimen required. Patients with PD often have their medication administered inappropriately in the acute care setting (e.g., holding a PD medication in preparation for surgery, not administering the medication on the patient's home schedule, and delaying administration). The research question posed in this study was the following: does a PD medication educational intervention in the clinical setting enhance knowledge, comfort, and competence of practicing nurses in the care of patients with PD regarding their medication safety?

Design

A mixed methods study design was used for this 5-month, two-part study with a sample of practicing RNs at three different hospitals. Part one of the study assessed nurses' initial knowledge of PD and PD medication safety and included an educational intervention. Part two of the study occurred 3 months later and evaluated if knowledge from the educational intervention was retained.

Methods

The study was conducted in two parts and included a pre-test, educational intervention, post-test, and follow-up test 3 months later. The educational intervention consisted of a 15-minute video of two PD advanced practice nurses being interviewed regarding the general care of a patient with PD. The pre-test, post-test, and follow-up test were identical and consisted of six questions regarding knowledge, comfort, and self-perceived competency. Participants were additionally asked three open-ended questions at follow-up to gain insight on the effectiveness of the educational intervention.

Results

A total sample of 252 RNs participated in this study. Statistically significant improvements in knowledge, comfort, and self-perceived competency were observed in the post-test scores compared to pre-test scores. These statistically significant improvements were retained after 3 months, despite a 42.9% decrease in the number of responders (n = 252 vs. n = 144). Additionally, compared to the post-test, there were no statistically significant declines in knowledge, comfort, or competency in the follow-up test. Qualitative findings indicated that the training regarding PD medications was retained and found to be valuable, even if it was seldom applied in practice.

Conclusion

A review of the literature and this study both support the need for increased education for practicing nurses as it relates to PD and PD medication safety. Healthcare systems, organizations, and associations that support continuing education for nurses create a stronger workforce. Education has been found to keep nurses up to date on the latest advances in care and treatment while also providing exposure to other areas of nursing beyond their clinical settings.

Clinical Relevance

Promoting better patient outcomes through safe medication administration is a hallmark of nursing care excellence. This study found that supporting the use of an educational intervention of PD medication safety for nurses improved RN levels of knowledge, comfort, and competency up to 3 months later. As the population of those with PD increases, healthcare systems, and nurses must now, more than ever, be poised to care for these individuals. This is a critical point in PD patient care since persons with PD are hospitalized 1.5 times more than their peers without PD.

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