Age-Related Changes in Visual Spatial Working Memory Cognits: Frontal-Parietal EEG Coherence During Delay

This study explored changes in scalp electrophysiology across two Working Memory (WM) tasks and two age groups. Continuous electroencephalography (EEG) was recorded from 18 healthy adults (18-34 years) and 12 healthy adolescents (14-17) during the performance of two Oculomotor Delayed Response (ODR) WM tasks; (i.e. eye movements were the metric of motor response). Delay-period, EEG data in the alpha frequency was sampled from anterior and parietal scalp sites to achieve a general measure of frontal and parietal activity, respectively. Frontal-parietal, alpha coherence was calculated for each participant for each ODR-WM task. Coherence significantly decreased in adults moving across the two ODR tasks, whereas, coherence significantly increased in adolescents moving across the two ODR tasks. The effects of task in the adolescent and adult groups were large and medium, respectively. Within the limits of this study, the results provide empirical support that WM development during adolescence include complex, qualitative, change

Canadianizing and Evaluating a Virtual Simulation Program for Community Health

Nurse educators are looking to integrate innovative pedagogies to enable students to acquire required competencies in community/population health nursing. Previously, nursing students who used Sentinel City® an American-based virtual simulation program for community health clinical learning have been shown to obtain equal or better learning outcomes compared to students who used traditional methods. To improve the fidelity of this virtual simulation program for our Canadian context, we Canadianized Sentinel City® to improve Canadian students learning experiences further. The purpose of this research was to describe the development of Sentinel City® Canada and subsequent evaluation of student learning outcomes after implementation across different sites in two provinces in Canada. Guided by constructivist and experiential learning concepts, we used a mixed-methods, cross-sectional survey. The quantitative questions were analysed using descriptive statistics. Inferential (ANOVA) statistics examined the relationship between the use of Sentinel City® Canada and ability to meet their course learning outcomes. Qualitative data was analyzed using thematic analysis following a six-step process including: 1) Become familiar with the data; 2) Generate initial codes; 3) Search for themes; 4); Review themes; 5) Define themes; and 6) Write up the findings. The study population included all currently registered nursing students (n=396) in post-secondary nursing programs at two universities and one college during the 2021/2022 academic year who completed their community/public/population health nursing clinical with the use of Sentinel City® Canada. The response rate was 18% (n=72). Learning outcomes of students who used Sentinel City® Canada varied across jurisdictions. The overall mean of students indicating that Sentinel City® Canada helped them achieve course objectives has increased from our previous studies. In fact, the overall mean of students indicating that Sentinel City® Canada helped them achieve course objectives has increased from our previous studies, with a mean of 2.47 in 2020, to a mean of 3.11 in 2022, to a mean of 3.34 with the Canadian version. Qualitative responses provide further insight into students’ perceptions. Canadianizing Sentinel City® has increased the fidelity of this community/population health simulation program and contributed to increasing student learning outcomes. Our findings provide evidence that Sentinel City® Canada can be a valuable learning tool for community/population health nursing clinical education that contributes to course learning outcomes. Résumé Les professeures et professeurs en sciences infirmières cherchent à intégrer des stratégies pédagogiques novatrices pour permettre aux étudiantes et étudiants de développer les compétences requises en soins infirmiers de santé communautaire/populationnelle. Auparavant, il a été démontré que les étudiantes et étudiants en sciences infirmières qui utilisaient Sentinel City, un programme américain de simulation virtuelle pour l’apprentissage clinique en santé communautaire, obtenaient des résultats d’apprentissage égaux ou supérieurs à ceux des étudiantes et étudiants qui étaient exposés à des méthodes traditionnelles. Afin d’accroitre la fidélité de ce programme de simulation virtuelle à notre contexte canadien, nous avons canadianisé Sentinel City dans le but d’améliorer davantage les expériences d’apprentissage des étudiantes et étudiants canadiens. Le but de cette recherche était de décrire la conceptualisation de Sentinel City Canada et l’évaluation ultérieure des résultats d’apprentissage des étudiantes et étudiants après sa mise en œuvre dans différents campus de deux provinces du Canada. Guidées par des concepts constructivistes et expérientiels d’apprentissage, nous avons mené une étude transversale à méthodes mixtes. Les réponses aux questions quantitatives ont été analysées à l’aide de statistiques descriptives. Les statistiques inférentielles (analyse de la variance) ont examiné la relation entre l’utilisation de Sentinel City Canada et la capacité à atteindre les résultats d’apprentissage des cours. Les données qualitatives ont été analysées à l’aide d’une analyse thématique suivant un processus en six étapes comprenant : 1) se familiariser avec les données; 2) générer les codes initiaux; 3) chercher des thèmes; 4) raffiner les thèmes; 5) définir les thèmes; et 6) rédiger les résultats. La population étudiée comprenait toutes les étudiantes et tous les étudiants en sciences infirmières actuellement inscrits (n = 396) dans des programmes de sciences infirmières dans deux universités et un site collégial d’un programme universitaire collaboratif au cours de l’année 2021-2022 et qui ont terminé leur formation clinique de soins infirmiers en santé communautaire/publique/ populationnelle avec l’utilisation de Sentinel City Canada. Le taux de réponse était de 18 % (n=72). Les résultats d’apprentissage des étudiantes et étudiants qui ont utilisé Sentinel City Canada variaient selon les régions. En fait, la moyenne globale des étudiantes et étudiants qui ont indiqué que Sentinel City Canada les a aidés à atteindre les objectifs du cours a augmenté par rapport à nos études précédentes, la moyenne passant de 2,47 en 2020, à 3,11 en 2022, puis à 3,34 avec la version canadienne. Les réponses qualitatives fournissent un aperçu plus approfondi des perceptions des étudiantes et étudiants. La canadianisation de Sentinel City a accru la fidélité de ce programme de simulation sur la santé communautaire/ populationnelle et a contribué à améliorer les résultats d’apprentissage des étudiantes et étudiants. Nos résultats indiquent que Sentinel City Canada peut être un outil d’apprentissage précieux pour la formation clinique en soins infirmiers de santé communautaire/ populationnelle qui contribue à atteindre les résultats d’apprentissage des cours

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation

Transcriptional memory-like imprints and enhanced functional activity in gamma delta T cells following resolution of malaria infection

Gamma delta T cells play an essential role in the immune response to many pathogens, including Plasmodium. However, long-lasting effects of infection on the gamma delta T cell population still remain inadequately understood. This study focused on assessing molecular and functional changes that persist in the gamma delta T cell population following resolution of malaria infection. We investigated transcriptional changes and memory-like functional capacity of malaria pre-exposed gamma delta T cells using a Plasmodium chabaudi infection model. We show that multiple genes associated with effector function (chemokines, cytokines and cytotoxicity) and antigen-presentation were upregulated in P. chabaudi-exposed gamma delta T cells compared to gamma delta T cells from naive mice. This transcriptional profile was positively correlated with profiles observed in conventional memory CD8(+) T cells and was accompanied by enhanced reactivation upon secondary encounter with Plasmodium-infected red blood cells in vitro. Collectively our data demonstrate that Plasmodium exposure result in "memory-like imprints" in the gamma delta T cell population and also promotes gamma delta T cells that can support antigen-presentation during subsequent infections

Airway macrophages display decreased expression of receptors mediating and regulating scavenging in early cystic fibrosis lung disease

Background: Cystic fibrosis (CF) airway disease is characterized by chronic inflammation, featuring neutrophil influx to the lumen. Airway macrophages (AMs) can promote both inflammation and resolution, and are thus critical to maintaining and restoring homeostasis. CF AM functions, specifically scavenging activity and resolution of inflammation, have been shown to be impaired, yet underlying processes remain unknown. We hypothesized that impaired CF AM function results from an altered expression of receptors that mediate or regulate scavenging, and set out to investigate changes in expression of these markers during the early stages of CF lung disease. Methods: Bronchoalveolar lavage fluid (BALF) was collected from 50 children with CF aged 1, 3 or 5 years. BALF cells were analyzed using flow cytometry. Expression levels of surface markers on AMs were expressed as median fluorescence intensities (MFI) or percentage of AMs positive for these markers. The effect of age and neutrophilic inflammation, among other variables, on marker expression was assessed with a multivariate linear regression model.Results: AM expression of scavenger receptor CD163 decreased with age (p = 0.016) and was negatively correlated with BALF %neutrophils (r = -0.34, p = 0.016). AM expression of immune checkpoint molecule SIRPα also decreased with age (p = 0.0006), but did not correlate with BALF %neutrophils. Percentage of AMs expressing lipid scavenger CD36 was low overall (mean 20.1% ± 16.5) and did not correlate with other factors. Conversely, expression of immune checkpoint PD-1 was observed on the majority of AMs (mean PD-1pos 72.9% ± 11.8), but it, too, was not affected by age or BALF %neutrophils. Compared to matched blood monocytes, AMs had a higher expression of CD16, CD91, and PD-1, and a lower expression of CD163, SIRPα and CD36. Conclusion: In BALF of preschool children with CF, higher age and/or increased neutrophilic inflammation coincided with decreased expression of scavenger receptors on AMs. Expression of scavenging receptors and regulators showed a distinctly different pattern in AMs compared to blood monocytes. These findings suggest AM capacity to counter inflammation and promote homeostasis reduces during initiation of CF airway disease and highlight new avenues of investigation into impaired CF AM function.</p

Decreased bioefficacy of long-lasting insecticidal nets and the resurgence of malaria in Papua New Guinea

Papua New Guinea (PNG) has the highest malaria transmission outside of Africa. Longlasting insecticidal nets (LLINs) are believed to have helped to reduce average malaria prevalence in PNG from 16% in 2008 to 1% in 2014. Since 2015 malaria in PNG has resurged significantly. Here, we present observations documenting decreased bioefficacy of unused LLINs with manufacturing dates between 2013 and 2019 collected from villages and LLIN distributors in PNG. Specifically, we show that of n = 167 tested LLINs manufactured after 2013, only 17% are fulfilling the required World Health Organisation bioefficacy standards of ≥ 80% 24 h mortality or ≥ 95% 60 min knockdown in bioassays with pyrethroid susceptible Anopheles farauti mosquitoes. In contrast, all (100%, n = 25) LLINs with manufacturing dates prior to 2013 are meeting these bioefficacy standards. These results suggest that decreased bioefficacy of LLINs is contributing to the malaria resurgence in PNG and of LLIN quality is warranted

Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism

Cardiosphere-derived cells (CDCs), which can be isolated from heart explants, are a promising candidate cell source for infarcted myocardium regeneration. However, current protocols used to expand CDCs require at least 1 month in vitro to obtain sufficient cells for transplantation. We report that CDC culture can be optimized by preconditioning the cells under hypoxia (2% oxygen), which may reflect the physiological oxygen level of the stem cell niche. Under hypoxia, the CDC proliferation rate increased by 1.4-fold, generating 6 × 10(6) CDCs with higher expression of cardiac stem cell and pluripotency gene markers compared to normoxia. Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were increased under hypoxia. Hypoxic preconditioning was mimicked by treatment with two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (BIC). Despite the difference in specificity, both PHDIs significantly increased c-Kit expression and activated HIF, EPO, and CXCR-4. Furthermore, treatment with PHDIs for 24 h increased cell proliferation. Notably, all hypoxic and PHDI-preconditioned CDCs had decreased oxygen consumption and increased glycolytic metabolism. In conclusion, cells cultured under hypoxia could have potentially enhanced therapeutic potential, which can be mimicked, in part, by PHDIs

Differential Patterns of Infection and Disease with P. falciparum and P. vivax in Young Papua New Guinean Children

BACKGROUND: Where P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season. CONCLUSIONS/SIGNIFICANCE: Under high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2(nd) and 3(rd) year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections

Effects of interventions on depression and anxiety in older people with physical health problems in the criminal justice system : a systematic review

The demand for health care in older people involved in the criminal justice system is high. The prevalence of mental and physical health conditions for people living in prison is greater than in community populations. After systematically searching 21 databases, we found no targeted interventions to support depression or anxiety for this group of people. 24 studies (including interventions of yoga, creative-arts-based programmes, positive psychology, or mindfulness-based interventions and psychotherapy) did contain people older than 50 years, but this only represented a minority (10%) of the overall study population. No single study reported outcomes of physical health. Future interventions need to consider the needs and views of this vulnerable group. Specific gendered and coproduced interventions are required to enhance the implementation, feasibility, and acceptability of interventions that are delivered in prisons

On the pivotal role of PPARa in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury

The role of peroxisome proliferator activated alpha (PPARα) -mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 weeks before in vivo contractile function was measured using cine magnetic resonance (MR) imaging. In isolated, perfused hearts, energetics were measured using 31P MR spectroscopy and glycolysis and fatty acid oxidation were measured using 3H labelling. Compared with normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation and mitochondrial UCP3 levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations and thereby ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation and UCP3 levels, with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high fat diet, with the result that ATP concentrations and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have already occurred in PPARα-/- mouse hearts, and sustained function in hypoxia despite an inability for further metabolic remodelling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodelling in hypoxia, but is prevented by dietary fat