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Longitudinal MRI and <sup>1</sup>H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction

by Jean-Baptiste Pérot, Anna Niewiadomska-Cimicka, Emmanuel Brouillet, Yvon Trottier, Julien Flament

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance. To characterize the temporal progression of brain degeneration of this model, we performed a longitudinal study spanning from early to late symptomatic stages using high-resolution magnetic resonance imaging (MRI) and in vivo 1H-magnetic resonance spectroscopy (1H-MRS). Compared to wild-type mouse littermates, MRI analysis of SCA7 mice shows progressive atrophy of defined brain structures, with the striatum, thalamus and cortex being the first and most severely affected. The volume loss of these structures coincided with increased motor impairments in SCA7 mice, suggesting an alteration of the sensory-motor network, as observed in SCA7 patients. MRI also reveals atrophy of the hippocampus and anterior commissure at mid-symptomatic stage and the midbrain and brain stem at late stage. 1H-MRS of hippocampus, a brain region previously shown to be dysfunctional in patients, reveals early and progressive metabolic alterations in SCA7 mice. Interestingly, abnormal glutamine accumulation precedes the hippocampal atrophy and the reduction in myo-inositol and total N-acetyl-aspartate concentrations, two markers of glial and neuronal damage, respectively. Together, our results indicate that non-cerebellar alterations and glial and neuronal metabolic impairments may play a crucial role in the development of SCA7 mouse pathology, particularly at early stages of the disease. Degenerative features of forebrain structures in SCA7 mice correspond to current observations made in patients. Our study thus provides potential biomarkers that could be used for the evaluation of future therapeutic trials using the SCA7140Q/5Q model.

A longitudinal investigation of structural empowerment profiles among healthcare employees

Abstract

Purpose

Research on structural empowerment has typically adopted a variable-centered perspective, which is not ideal to study the combined effects of structural empowerment components. This person-centered investigation aims to enhance our knowledge about the configurations, or profiles, of healthcare employees' perceptions of the structural empowerment dimensions present in their workplace (opportunity, information, support, and resources). Furthermore, this study considers the replicability and stability of these profiles over a period of 2 years, and their outcomes (perceived quality of care, and positive and negative affect).

Design

Participants completed the same self-reported questionnaires twice, 2 years apart.

Methods

A sample of 633 healthcare employees (including a majority of nurses and nursing assistants) participated. Latent transition analyses were performed.

Results

Five profiles were identified: Low Empowerment, High Information, Normative, Moderately High Empowerment, and High Empowerment. Membership into the Normative and Moderately High Empowerment profiles demonstrated a high level of stability over time (79.1% to 83.2%). Membership in the other profiles was either moderately stable (43.5% for the High Empowerment profile) or relatively unstable (19.7% to 20.4% for the Low Empowerment and High Information profiles) over time. More desirable outcomes (i.e., higher positive affect and quality of care, and lower negative affect) were observed in the High Empowerment profile.

Conclusions

These results highlight the benefits of high structural empowerment, in line with prior studies suggesting that structural empowerment can act as a strong organizational resource capable of enhancing the functioning of healthcare professionals. These findings additionally demonstrate that profiles characterized by the highest or lowest levels of structural empowerment were less stable over time than those characterized by more moderate levels.

Clinical Relevance

From an intervention perspective, organizations and managers should pay special attention to employees perceiving low levels of structural empowerment, as they experience the worst outcomes. In addition, they should try to maintain high levels of structural empowerment within the High Empowerment profile, as this profile is associated with the most desirable consequences. Such attention should be fruitful, considering the instability of the High Empowerment and Low Empowerment profiles over time.

Registration

NCT04010773 on ClinicalTrials.gov (4 July, 2019).

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression

by Alexia Loste, Marc Clément, Sandrine Delbosc, Kevin Guedj, Jean Sénémaud, Anh-Thu Gaston, Marion Morvan, Guillaume Even, Grégory Gautier, Alexander Eggel, Michel Arock, Emanuele Procopio, Catherine Deschildre, Liliane Louedec, Jean-Baptiste Michel, Lydia Deschamps, Yves Castier, Raphaël Coscas, Jean-Marc Alsac, Pierre Launay, Giuseppina Caligiuri, Antonino Nicoletti, Marie Le Borgne

Aims

IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.

Methods and results

Through histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression.

Conclusions

Our data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.

Professionalism in pre‐licensure nursing education: Core values, didactic coursework and clinical training

Abstract

Aim

To discuss professionalism for pre-licensure nursing students and identify recommendations for inclusion in core values, didactic coursework and clinical training.

Background

Professionalism is part of the nursing identity that encompasses integrity and honesty. This concept has been difficult to translate into formal education in nursing programs and clinical practice.

Design

A discursive paper.

Data Sources

A search of national literature without date restrictions in PubMed, CINAHL, Google Scholar and frameworks for nursing education. We explored principles of professionalism in nursing education and practice.

Discussion

Evidence-based literature supports the integration of core values of altruism, autonomy, human dignity, integrity, honesty and social justice into didactic curricula, and clinical training. Principles of professionalism can be incorporated intentionally in nursing education to maintain patient safety and trust.

Conclusion

The principles of professionalism, related to core values of the nursing profession, are abundantly described in the literature. However, these principles represent core values that have not been formally conceptualized. With the changing landscape of healthcare, there is a need for deliberate, measurable integration of professionalism into pre-licensure education.

Patient or Public Contribution

There was no patient or public involvement in the design or drafting of this discursive paper.

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