Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

BACKGROUND: In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. METHODS: GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. RESULTS: PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). CONCLUSIONS: In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

An Interuniversity Competition for Medical Students to Learn Radiology in the Second Life Metaverse.

PURPOSE: The aim of this study was to evaluate an interuniversity competition online to learn radiology held in a 3-D virtual world, the Second Life metaverse, by analyzing the results of the game and students' perceptions. METHODS: Medical students voluntarily participated in teams of four, for 6 weeks, successively covering radiologic anatomy and radiologic semiology of the chest, abdomen, and musculoskeletal. Each week, participants had 4.5 days to study self-learning presentations and 2.5 days to complete an individual multiple-choice test and a team task, the results of which determined the game's ranking. Participants were asked to complete a cognitive-load test, a perception questionnaire, and a postexposure knowledge test. RESULTS: The competition was repeated for 2 years (editions), in 2020 and 2021. Seventy-five of 102 teams (73.5%) registered completed the game; 76% of them included third-year students. The average percentage of correct answers in the individual tests and team tasks was 74.2 ± 15.1 and 71.6 ± 14.7 respectively, without significant differences between both competitions. In general, the experience was valued positively (scores >8 on a 10-point scale). A lower perception score was found in 2021 among students from universities other than the organizing university, showing a positive correlation with the in-game score. CONCLUSIONS: An interuniversity competition in the Second Life metaverse for undergraduate learning radiology is feasible and reproducible. Participating medical students considered it interesting and useful and also identified this activity during the 2 years of the coronavirus disease 2019 pandemic as a playful learning and social interaction experience.

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy.

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFß1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.

Improving Oral Presentation Skills for Radiology Residents through Clinical Session Meetings in the Virtual World Second Life.

BACKGROUND: The objective of this study was to conduct a clinical session meeting in the virtual world of Second Life to improve the oral presentation skills of radiology residents and to assess the perception of the attendees. METHODS: A clinical session meeting (10 two-hour sessions over four weeks), where participants presented their own clinical sessions, followed by a turn of interventions by the attendees, was designed and carried out. Attendees were asked to complete an evaluation questionnaire. Descriptive statistics were performed. RESULTS: Twenty-eight radiology residents attended the meeting, and 23 (81.2%) completed the evaluation questionnaire; 95.7-100% of them agreed that the virtual environment was attractive and suitable for holding the meeting and that the content was appropriate for their training as residents. They rated with ≥8.9 points (from 1 to 10) different aspects of the experience, highlighting the role of teachers (9.7 ± 0.6) and the usefulness of their training (9.4 ± 0.9). CONCLUSIONS: Second Life can be used effectively to train oral communication skills in public, in an environment perceived as attractive and suitable for learning, through an experience described by the attendees as interesting and useful, highlighting the advantages of social contact with their peers.

Pleural empyema secondary to perforated diverticulosis due to biliary neoplasia infiltration.

A long-term female smoker presented to the emergency department with cough, greenish mucus and dyspnoea, without fever. The patient also reported abdominal pain and significant weight loss in recent months. Laboratory tests showed leucocytosis with neutrophilia, lactic acidosis and a faint left lower lobe consolidation on chest X-ray, for which she was admitted to the pneumology department and started on broad-spectrum antibiotherapy. After 3 days of clinical stability, the patient deteriorated rapidly, with worsening of analytical parameters and coma. The patient died a few hours later. Given the rapid and unexplained evolution of the disease, a clinical autopsy was requested, which revealed a left pleural empyema caused by perforated diverticula by neoplastic infiltration of biliary origin.

A team-based competition for undergraduate medical students to learn radiology within the virtual world Second Life.

BACKGROUND: A multi-user competitive game within the virtual world Second Life for undergraduate radiology learning was adapted for team participation. This study aimed to assess student perception, impact on learning, and eventual correlation of game results with post-exposure tests and course grades. METHODS: The game consisted of six weekly stages, dedicated to thoracic, abdominal, and musculoskeletal radiological anatomy and semiology. Participants had several days a week to review self-guided radiology educational content and then complete individual multiple-choice tests and solve team tasks to progress through the game's ranking. Additionally, they completed a cognitive load test, a questionnaire about the experience and a post-exposure knowledge test. RESULTS: Fifty-two students organised into 13 teams participated in the game and assessed different aspects of the experience with a mean score ≥ 7.8 on a 10-point scale, highlighting the participation of the teacher (9.3 ± 1.1), the educational contents (8.8 ± 1.4) and the usefulness for their education (8.7 ± 1.4). Participants obtained better post-exposure test results (p < 0.007) and better course grades (p < 0.021) than non-participants did. CONCLUSION: A multi-user game adapted to team competition to learn radiology in Second Life was very positively perceived by third-year medical students, who highly valued its content, organisation, and usefulness for their training. Most of the participants agreed that they had collaborated as a team and that playing in competitive environments helps them learn better. The best post-exposure and academic results compared to non-participating students indicate the potential impact of the game on learning.

A Distinct Metabolite Profile Correlates with Neurodegenerative Conditions and the Severity of Congenital Hydrocephalus.

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated with increased intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage, and astrocytic reaction. The aim of this study was to identify whether a metabolite profile revealing tissue responses according to the severity of hydrocephalus can be detected. The hyh mutant mouse used for this study exhibits 2 different forms of hydrocephalus, severe and moderate. In a comprehensive investigation into the 2 progressions of hydrocephalus, mice with severe hydrocephalus were found to have higher ICP and astrocytic reaction. Several metabolites from the mouse brain cortex were analyzed with 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR) spectroscopy. A differential profile for metabolites including glutamate and glutamine was found to correlate with the severity of hydrocephalus and can be explained due to differential astrocytic reactions, neurodegenerative conditions, and the presence of ischemia. The glutamate transporter EAAT2 and the metabolite taurine were found to be key histopathological markers of affected parenchymata. In conclusion, a differential metabolite profile can be detected according to the severity of hydrocephalus and associated ICP and therefore can be used to monitor the efficacy of experimental therapies.

Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage.

To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.