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Paola Ferri,1 Serena Stifani,2 Elena Morotti,2 Maria Nuvoletta,3 Loris Bonetti,4 Sergio Rovesti,1 Anna Cutino,5 Rosaria Di Lorenzo6 1Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy; 2School of Nursing, University of Modena and Reggio Emilia, Modena 41124, Italy; 3Occupational Medicine, Maserati SPA, Modena 41121, Italy; 4Nursing Research and Development Unit, Oncology Institute of Southern Switzerland, Bellinzona 6500, Switzerland; 5Psychiatry, University of Modena and Reggio Emilia, Modena 41124, Italy; 6Psychiatric Intensive Treatment Facility, Mental Health and Drug Abuse Department of AUSL-Modena, Modena 41122, ItalyCorrespondence: Paola FerriDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, via Campi, 287, Modena 41125, ItalyEmail paola.ferri@unimore.itIntroduction: Increase in the knowledge of “caring science” among nurses plays a key role in ensuring a correct caring behavior towards patients. Caring training for students is a priority in nursing education, but unfortunately there are limited and conflicting studies which explore this outcome. The purpose of this observational study was to explore the perceptions of caring behaviors by nursing students during their clinical practice training in order to highlight if the level of caring behaviors changes as the nursing course progresses.Materials and Methods: The Caring Behaviors Inventory-24 (CBI-24) was administered to 331 students, enrolled in the three years of an Italian Nursing Course, who accepted to participate in the study (89.2% response rate). The data were analyzed using SPSS software version 26.0 (SPSS Inc., Chicago, IL).Results: The total mean score of CBI-24 was 4.82 in the first, 5.12 in the second and 5.26 in the third-year students. The CBI-24 dimensions “Responding to individual needs” and “Being with” obtained the highest scores among the students of the first year. At the end of the first year, our students were already able to perform expressive caring, whereas instrumental caring developed at a high level in the second and third years. We did not highlight any statistically significant difference between the two gender CBI-24 item scores.Conclusion: In light of our results, we put in evidence that Nursing Degree Programme favours the development in students of both relational and technical components of caring behaviors. We hope that in future students’ self-assessment of caring behaviors could be considered an educational outcome for Nursing Programme.Keywords: Caring Behaviors Inventory, caring, expressive caring, instrumental caring, nursing education, nursing students

Rhabdomyosarcoma (RMS) is a paediatric soft-tissue sarcoma arising from skeletal muscle precursors coexpressing markers of proliferation and differentiation. Inducers of myogenic differentiation suppress RMS tumourigenic phenotype. The Notch target gene HES1 is upregulated in RMS and prevents tumour cell differentiation in a Notch-dependent manner. However, Notch receptors regulating this phenomenon are unknown. In agreement with data in RMS primary tumours, we show here that the Notch3 receptor is overexpressed in RMS cell lines versus normal myoblasts. Notch3-targeted downregulation in RMS cells induces hyper-phosphorylation of p38 and Akt essential for myogenesis, resulting in the differentiation of tumour cells into multinucleated myotubes expressing Myosin Heavy Chain. These phenomena are associated to a marked decrease in HES1 expression, an increase in p21Cip1 level and the accumulation of RMS cells in the G1 phase. HES1-forced overexpression in RMS cells reverses, at least in part, the pro-differentiative effects of Notch3 downregulation. Notch3 depletion also reduces the tumourigenic potential of RMS cells both in vitro and in vivo. These results indicate that downregulation of Notch3 is sufficient to force RMS cells into completing a correct full myogenic program providing evidence that it contributes, partially through HES1 sustained expression, to their malignant phenotype. Moreover, they suggest Notch3 as a novel potential target in human RMS. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive death of motor neurons (MNs). Glial cells play roles in MN degeneration in ALS. More specifically, astrocytes with mutations in the ALS-associated gene Cu/Zn superoxide dismutase 1 (SOD1) promote MN death. The mechanisms by which SOD1-mutated astrocytes reduce MN survival are incompletely understood. To characterize the impact of SOD1 mutations on astrocyte physiology, we generated astrocytes from human induced pluripotent stem cell (iPSC) derived from ALS patients carrying SOD1 mutations, together with control isogenic iPSCs. We report that astrocytes harboring SOD1(A4V) and SOD1(D90A) mutations exhibit molecular and morphological changes indicative of reactive astrogliosis when compared to isogenic astrocytes. We show further that a number of nuclear phenotypes precede, or coincide with, reactive transformation. These include increased nuclear oxidative stress and DNA damage, and accumulation of the SOD1 protein in the nucleus. These findings reveal early cell-autonomous phenotypes in SOD1-mutated astrocytes that may contribute to the acquisition of a reactive phenotype involved in alterations of astrocyte-MN communication in ALS., (© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an adeno-associated virus (AAV)-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting chromatin remodelers in reactive gliosis and neuroinflammation in injury and neurological diseases., Competing Interests: Declaration of interests T.I. is a co-founder, member of the advisory board, and has an equity interest in Data4Cure and Serinus Biosciences. He is a consultant for and has an equity interest in Ideaya BioSciences and Light Horse Therapeutics. The terms of these arrangements have been reviewed and approved by University of California, San Diego in accordance with its conflict of interest policies. N.E.S. is an adviser to Qiagen and a co-founder of and adviser to TruEdit Bio and OverT Bio., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The fatal motor neuron (MN) disease Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive MN degeneration. Phrenic MNs (phMNs) controlling the activity of the diaphragm are prone to degeneration in ALS, leading to death by respiratory failure. Understanding of the mechanisms of phMN degeneration in ALS is limited, mainly because human experimental models to study phMNs are lacking. Here we describe a method enabling the derivation of phrenic-like MNs from human iPSCs (hiPSC-phMNs) within 30 days. This protocol uses an optimized combination of small molecules followed by cell-sorting based on a cell-surface protein enriched in hiPSC-phMNs, and is highly reproducible using several hiPSC lines. We show further that hiPSC-phMNs harbouring ALS-associated amplification of the C9orf72 gene progressively lose their electrophysiological activity and undergo increased death compared to isogenic controls. These studies establish a previously unavailable protocol to generate human phMNs offering a disease-relevant system to study mechanisms of respiratory MN dysfunction., (© 2024. The Author(s).)

Background and Aim: The COVID-19 pandemic has required a rapid reorganization of clinical training and supervision models for nursing education. The aim of this study was to compare students' levels of perception of the quality of the Clinical Learning Environment (CLE) using two different clinical supervision models., Methods: A comparative design was implemented. A convenience sample of second and third-year undergraduate nursing students (n=127) in clinical training in the 2018/2019 Academic Year (AY) received the usual nursing staff supervision model, while during the COVID-19 pandemic in the following year, they (n=69) received an individualized supervision model. Data were collected using three instruments: the Clinical Learning Environmental Quality Evaluation Index (CLEQI); the Clinical Learning Environment, Supervision and Nurse Teacher Scale (CLES+T); and a socio-demographic tool., Results: The mean total scores of both scales had increased in the second survey (CLEQI: M=57.88±11.8 vs. M=60.88±9.3, p=0.035; CLES+T: M=148.4±23.3 vs. M=154.5±21.9, p=0.037). The nursing students reported high levels of CLE quality with both supervision models, even though the individualized supervision model was rated significantly higher by the students than the staff supervision model., Conclusions: Students supported by a personal supervisor during clinical training had a more positive experience and rated the quality of the tutorial strategies, learning opportunities, safety and nursing care, leadership style of the ward manager and overall CLE more highly.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder caused by progressive loss of motor neurons and there is currently no effective therapy. Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein 43 kDa (TDP-43) within the CNS is a pathological hallmark in sporadic ALS and prion-like propagation of pathogenic TDP-43 is thought to be implicated in disease progression. However, cell-to-cell transmission of pathogenic TDP-43 in the human CNS has not been confirmed experimentally. Here we used induced pluripotent stem cells (iPSCs)-derived cerebral organoids as recipient CNS tissue model that are anatomically relevant human brain. We injected postmortem spinal cord protein extracts individually from three non-ALS or five sporadic ALS patients containing pathogenic TDP-43 into the cerebral organoids to validate the templated propagation and spreading of TDP-43 pathology in human CNS tissue. We first demonstrated that the administration of spinal cord extracts from an ALS patient induced the formation of TDP-43 pathology that progressively spread in a time-dependent manner in cerebral organoids, suggesting that pathogenic TDP-43 from ALS functioned as seeds and propagated cell-to-cell to form de novo TDP-43 pathology. We also reported that the administration of ALS patient-derived protein extracts caused astrocyte proliferation to form astrogliosis in cerebral organoids, reproducing the pathological feature seen in ALS. Moreover, we showed pathogenic TDP-43 induced cellular apoptosis and that TDP-43 pathology correlated with genomic damage due to DNA double-strand breaks. Thus, our results provide evidence that patient-derived pathogenic TDP-43 can mimic the prion-like propagation of TDP-43 pathology in human CNS tissue. Our findings indicate that our assays with human cerebral organoids that replicate ALS pathophysiology have a promising strategy for creating readouts that could be used in future drug discovery efforts against ALS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tamaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Astrocytes play important roles in the function and survival of neuronal cells. Dysfunctions of astrocytes are associated with numerous disorders and diseases of the nervous system, including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Human-induced pluripotent stem cell (iPSC)-based approaches are becoming increasingly important for the study of the mechanisms underlying the involvement of astrocytes in non-cell autonomous processes of motor neuron degeneration in ALS. These studies must account for the molecular and functional diversity among astrocytes in different regions of the brain and spinal cord. It is essential that the most pathologically relevant astrocyte preparations are used when investigating non-cell autonomous mechanisms of either upper or lower motor neuron degeneration in ALS. Here, we describe the efficient and streamlined generation of human iPSC-derived astrocytes with molecular and biological properties similar to physiological astrocytes in the ventral spinal cord. These induced astrocytes exhibit spontaneous and ATP-induced calcium transients, and lack signs of overt activation. Human iPSC-derived astrocytes with ventral spinal cord features offer advantages over more generic astrocyte preparations for the study of both ventral spinal cord astrocyte biology and the involvement of astrocytes in mechanisms of lower motor neuron degeneration in ALS.

As the resident immune cells of the healthy nervous system, homeostatic microglia can rapidly become activated in response to injury/disease. Dysregulated microglia activation is a hallmark of nervous system disorders including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. The elucidation of the biological and pathological roles of microglia has recently benefitted from the development of microglia-like cells using human induced pluripotent stem cell (iPSC)-based approaches. The success of iPSC-derived microglia preparations as a disease-relevant model system depends on their representation of the in vivo spatial and temporal heterogeneity of microglia under pathological conditions. Little is currently known about the potential of human iPSC-derived microglia generated using different methods for the study of neurodegenerative diseases. We compared the transcriptomes of human iPSC-derived microglia generated using two frequently used in vitro differentiation methods to determine whether separate strategies can generate microglia with distinct transcriptional signatures in vitro . We show that microglia derived using different differentiation methods display distinct maturation characteristics after equivalent times in culture. We also reveal that iPSC-derived microglia preparations generated using these two methods are composed of different subpopulations with transcriptomic signatures resembling those of in vivo regionally distinct microglia subtypes, specifically white-matter and gray-matter microglia. These findings highlight the need to better characterize the subtype composition of each microglia preparation prior to its use to model neurodegenerative diseases.