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Intensive care unit (ICU) nurses frequently manually titrate norepinephrine to maintain a predefined mean arterial pressure (MAP) target after high-risk surgery. However, achieving this task is often suboptimal. We have developed a closed-loop vasopressor (CLV) controller to better maintain MAP within a narrow range. After ethical committee approval, fifty-three patients admitted to the ICU following high-risk abdominal surgery were randomized to CLV or manual norepinephrine titration. In both groups, the aim was to maintain MAP in the predefined target of 80-90 mmHg. Fluid administration was standardized in the two groups using an advanced hemodynamic monitoring device. The primary outcome of our study was the percentage of time patients were in the MAP target. Over the 2-hour study period, the percentage of time with MAP in target was greater in the CLV group than in the control group (median: IQR25-75: 80 [68-88]% vs. 42 [22-65]%), difference 37.2, 95% CI (23.0-49.2); p  90 mmHg was not statistically different between groups. In patients admitted to the ICU after high-risk abdominal surgery, closed-loop control of norepinephrine infusion better maintained a MAP target of 80 to 90 mmHg and significantly decreased postoperative hypotensive when compared to manual norepinephrine titration.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

Abstract Background Phylogenetics is one of the main methodologies to understand cross-cutting principles of evolution, such as common ancestry and speciation. Phylogenetic trees, however, are reportedly challenging to teach and learn. Furthermore, phylogenetics teaching methods traditionally rely solely on visual information, creating inaccessibility for people with visual impairment. Sensory learning style models advocate for tailoring teaching to individual preferred sensory learning style. However, recent research suggests that optimal learning, independently of preferred learning style, depends on the types of transmitted information and learning tasks. The lack of empirically-supported education into the effectiveness of teaching phylogenetics through alternative sensory modalities potentially hinders learning. The aim of this study was to determine whether phylogenetic trees could be better understood if presented in kinaesthetic or multisensory teaching modalities. Results Participants (N = 52) self-assessed personal learning style and were randomly assigned to: visual, kinaesthetic or multisensory learning conditions. Phylogeny reading performance was better for both kinaesthetic and multisensory teaching conditions, compared to the visual teaching condition. There was no main effect and no interaction effect of personal learning style. Conclusions This study establishes a baseline for further research by suggesting that easy-to-implement kinaesthetic teaching modalities might support phylogenetic tree learning and reading. This has practical implications for evolution education and accessibility for students with visual impairment, underscoring the need to shift from vision-centric teaching paradigms towards evidence-based instructional strategies that accommodate sensory diversity.

Floodplains are unique environments that provide a dynamic link between terrestrial and aquatic systems. Intensification of human activity – particularly agriculture and urbanisation – has resulted in the degradation of floodplains worldwide. Restoration and sustainable management of floodplains requires holistic assessment and compromise between stakeholders to successfully balance environmental, economic, and social benefits. Yet, understanding these complex systems sufficiently to provide evidence-based recommendations is a challenge. We present the lessons learned from establishing an interdisciplinary research-based framework on the agricultural floodplain of Lake Saint Pierre, Québec, Canada, whose mandate was to a) understand and define key environmental, agricultural, and socioeconomic attributes of the landscape, b) quantify the trade-offs and synergies between these attributes across different agricultural practices, regions, and land uses, and c) explore novel agri-environmental management practices to assess their role in sustainable floodplain management. Within this manuscript, we explore the benefits that such an approach offers in evaluating sustainable floodplain land use. We found that an interdisciplinary research-based approach demonstrated important benefits such as knowledge transfer, more efficient use of resources (e.g., personnel, funding), and a flexible yet robust research framework. A framework of individual research projects connected to broader interdisciplinary themes allowed a more holistic synthesis of the floodplain systems and assessment of agri-environmental practices. By implicitly considering spatial and social scales, we conceptualised not just how redistribution of the land use types can meet sustainable management objectives, but also explored how compromises within existing uses can optimise socio-economic, agricultural and environmental dimensions and move towards a sustainable multifunctional landscape.

Abstract Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Abstract Accumulation of immune cells and proteins in the subarachnoid space (SAS) is found during multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis (EAE). Whether the flow of cerebrospinal fluid (CSF) along the SAS of the spinal cord is impacted is yet unknown. Combining intravital near-infrared (NIR) imaging with histopathological analyses, we observed a significantly impaired bulk flow of CSF tracers within the SAS of the spinal cord prior to EAE onset, which persisted until peak stage and was only partially recovered during chronic disease. The impairment of spinal CSF flow coincided with the appearance of fibrin aggregates in the SAS, however, it preceded immune cell infiltration and breakdown of the glia limitans superficialis. Conversely, cranial CSF efflux to cervical lymph nodes was not altered during the disease course. Our study highlights an early and persistent impairment of spinal CSF flow and suggests it as a sensitive imaging biomarker for pathological changes within the leptomeninges.

Abstract Background Evidence is needed to understand factors that influence child development and caregiving experiences, especially in marginalized contexts, to inform the development and implementation of early childhood development (ECD) interventions. This study explores caregiving practices for young children in an urban informal settlement with Kenyans and embedded refugees, and identifies factors shaping these caregiving experiences, to inform the design and development of potentially appropriate ECD interventions. Methods A qualitative formative study, which included 14 focus group discussions (n = 125 participants), and 13 key informant interviews was conducted between August and October 2018. Purposive sampling approaches were used to select a diverse range of respondents including caregivers of children below three years of age and stakeholders of Kenyan nationality and refugees. Data were analysed using a thematic approach and the Nurturing Care Framework was used as an interpretative lens. Results There was a fusion of traditional, religious and modern practices in the care for young children, influenced by the caregivers’ culture, and financial disposition. There were mixed views/practices on nutrition for young children. For example, while there was recognition of the value for breastfeeding, working mothers, especially in the informal economy, found it a difficult practice. Stimulation through play was common, especially for older children, but gaps were identified in aspects such as reading, and storytelling in the home environment. Some barriers identified included the limited availability of a caregiver, insecurity, and confined space in the informal settlement, all of which made it difficult for children to engage in play activities. Physical and psychological forms of discipline were commonly mentioned, although few caregivers practiced and recognized the need for using non-violent approaches. Some overarching challenges for caregivers were unemployment or unstable sources of income, and, particularly for refugee caregivers, their legal status. Conclusion These findings point to the interplay of various factors affecting optimal caregiving for young children in an urban informal settlement with Kenyans and refugees. Integrated ECD interventions are needed for such a mixed population, especially those that strive to anchor along caregivers’ social support system, co-designed together with community stakeholders, that ideally focus on parent skills training promoting nurturing care and economic empowerment.

This article focuses on the relationship between coursework and field experience, theory and practice. Guided by Korthagen et al.'s (2006) fundamental principles for teacher education, an alternative student teaching structure was tested at the Universite´ du Que´bec en Outaouais (Canada) in the Fall 2016 term. An online survey was conducted to elicit feedback on how this structure helped enhance the link between theory and practice, according to student teachers, mentor teachers, and teacher educators. Results show the structure offered student teachers the opportunity to reinvest learning in both theory and practice and to discuss the tensions between the two, which represented a significant moment in the program's development.

In their recent article on teachers' proportional reasoning, Copur-Gencturk et al. (2022) draw attention to a type of strategy that they call "relative", lodged right between additive and multiplicative thinking. This strategy raised interest in our research team, as it aligned well and helped give stronger meaning to some strategies obtained during a series of individual interviews on solving proportionality tasks. Using that "relative proportional reasoning" lens, this article explores several strategies engaged in by two students (11 and 13 years old) and in doing so outlines a number of dimensions about proportional reasoning that these strategies enable to draw out. The detailed consideration of this relative proportional reasoning raises important questions as to its possible role in the difficult transition from additive to multiplicative thinking in proportionality, opening the door to further inquiries on these matters.

Meninges cover the surface of the brain and spinal cord and contribute to protection and immune surveillance of the central nervous system (CNS). How the meningeal layers establish CNS compartments with different accessibility to immune cells and immune mediators is, however, not well understood. Here, using 2-photon imaging in female transgenic reporter mice, we describe VE-cadherin at intercellular junctions of arachnoid and pia mater cells that form the leptomeninges and border the subarachnoid space (SAS) filled with cerebrospinal fluid (CSF). VE-cadherin expression also marked a layer of Prox1+ cells located within the arachnoid beneath and separate from E-cadherin+ arachnoid barrier cells. In vivo imaging of the spinal cord and brain in female VE-cadherin-GFP reporter mice allowed for direct observation of accessibility of CSF derived tracers and T cells into the SAS bordered by the arachnoid and pia mater during health and neuroinflammation, and detection of volume changes of the SAS during CNS pathology. Together, the findings identified VE-cadherin as an informative landmark for in vivo imaging of the leptomeninges that can be used to visualize the borders of the SAS and thus potential barrier properties of the leptomeninges in controlling access of immune mediators and immune cells into the CNS during health and neuroinflammation.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells with innate-like antimicrobial responsiveness. MAIT cells are known for MR1 (MHC class I-related protein 1)-restricted recognition of microbial riboflavin metabolites giving them the capacity to respond to a broad range of microbes. However, recent progress has shown that MAIT cells can also respond to several viral infections in humans and in mouse models, ranging from HIV-1 and hepatitis viruses to influenza virus and SARS-CoV-2, in a primarily cognate Ag-independent manner. Depending on the disease context MAIT cells can provide direct or indirect antiviral protection for the host and may help recruit other immune cells, but they may also in some circumstances amplify inflammation and aggravate immunopathology. Furthermore, chronic viral infections are associated with varying degrees of functional and numerical MAIT cell impairment, suggesting secondary consequences for host defense. In this review, we summarize recent progress and highlight outstanding questions regarding the emerging role of MAIT cells in antiviral immunity.

Summary: Background: Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways. Methods: Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts. Findings: RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis. Interpretation: This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH. Funding: Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).