A novel locomotion-based prepulse inhibition assay in zebrafish larvae.

Sensory gating, measured using prepulse inhibition (PPI), is an endophenotype of neuropsychiatric disorders that can be assessed in larval zebrafish models. However, current PPI assays require high-speed cameras to capture rapid c-bend startle behaviours of the larvae. In this study, we designed and employed a PPI paradigm that uses locomotion as a read-out of zebrafish larval startle responses. PPI percentage was measured at a maximum of 87% and strongly reduced upon administration of the NMDA receptor antagonist, MK-801. This work provides the foundation for simpler and more accessible PPI assays using larval zebrafish to model key endophenotypes of neurodevelopmental disorders.

Areas of work-life, psychological capital and emotional intelligence on compassion fatigue and compassion satisfaction among nurses: A cross-sectional study.

AIM: To examine the impact of six areas of work-life, emotional intelligence and psychological capital on compassion fatigue and compassion satisfaction among Canadian Registered Nurses and licensed practical nurses. DESIGN: A cross-sectional survey study. METHODS: A convenience sample of 296 Registered Nurses and 110 licensed practical nurses answered a self-administered questionnaire measuring areas of work-life, psychological capital, emotional intelligence, compassion satisfaction and compassion fatigue in September 2019. The association between variables were analysed with descriptive and correlational analyses, while the hypothesized models were tested using multiple regression analyses. RESULTS: This study identified several areas of work-life and intrapersonal resources that impacted compassion satisfaction and compassion fatigue. Among Registered Nurses, compassion satisfaction was predicted by psychological capital, rewards, values and workload. Compassion fatigue was predicted by psychological capital, workload, control and community. Among licensed practical nurses, compassion satisfaction was predicted by psychological capital and emotional intelligence. Compassion fatigue was predicted by workload and psychological capital. Study results also revealed significant differences in Registered Nurses' and licensed practical nurses' perceptions of workload, rewards and fairness at work, and both compassion satisfaction and compassion fatigue. Registered Nurses perceived their workload to be more manageable and perceived greater rewards and greater fairness at work than licensed practical nurses. Compassion fatigue was higher for Registered Nurses than licensed practical nurses, while compassion satisfaction was higher for licensed practical nurses than Registered Nurses. Future studies should investigate the nature and span of these differences to suggest relevant strategies to mitigate compassion fatigue and promote compassion satisfaction for each of these nursing roles. CONCLUSION: The results of this study underscore the need to create nursing work environments that foster a manageable workload and positive social relationships, where nurses have professional autonomy, decision-making capacities and access to adequate resources to do their job effectively. The nursing work environment should also provide recognition of nurses' contributions and an alignment between personal and organizational values. Investments in the development and improvement of nurses' psychological capital and emotional intelligence should be prioritized since they are malleable and impactful intrapersonal resources on compassion satisfaction and compassion fatigue. REPORTING METHOD: This study adhered to the STROBE guidelines. PUBLIC CONTRIBUTION: A total of 406 nurses were involved in this study by answering a self-administered study survey.

Bi-directional signaling between the intestinal epithelium and type-3 innate lymphoid cells regulates secretory dynamics and interleukin-22.

Type-3 innate lymphoid cells (ILC3) respond to localized environmental cues to regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator and downstream target of ILC3 signaling, however, the complexity of mucosal tissues can hinder efforts to define specific interactions between these two compartments. Here, we employ a reductionist co-culture system of murine epithelial small intestinal organoids (SIO) with ILC3 to uncover bi-directional signaling mechanisms that underlie intestinal homeostasis. We report that ILC3 induce global transcriptional changes in intestinal epithelial cells, driving the enrichment of secretory goblet cell signatures. We find that SIO enriched for goblet cells promote NKp46+ ILC3 and interleukin (IL)-22 expression, which can feedback to induce IL-22-mediated epithelial transcriptional signatures. However, we show that epithelial regulation of ILC3 in this system is contact-dependent and demonstrate a role for epithelial Delta-Like-Canonical-Notch-Ligand (Dll) in driving IL-22 production by ILC3, via subset-specific Notch1-mediated activation of T-bet+ ILC3. Finally, by interfering with Notch ligand-receptor dynamics, ILC3 appear to upregulate epithelial Atoh1 to skew secretory lineage determination in SIO-ILC3 co-cultures. This research outlines two complimentary bi-directional signaling modules between the intestinal epithelium and ILC3, which may be relevant in intestinal homeostasis and disease.

The Effect of a Standing Intervention on Falls in Long Term Care: a Secondary Analysis of a Randomized Controlled Trial.

Background: Older adults in long term care (LTC) spend over 90% of their day engaging in sedentary behaviour. Sedentary behaviour may exacerbate functional decline and frailty, increasing the risk for falls. The purpose of this study is to explore the impact of a 22-week standing intervention on falls among LTC residents at 12-month follow-up. Methods: This was a planned secondary analysis of the Stand if You Can randomized controlled trial. The original trial randomized 95 participants (n = 47 control; n = 48 intervention) to either a sitting control or a supervised standing intervention group (100 minutes/week) for 22 weeks. Falls data were available to be collected over 12 months post-intervention for 89 participants. The primary outcome was a hazard of fall (Yes/No) during the 12-month follow-up period. Results: A total of 89 participants (average age 86 years ± 8.05; 71.9% female) were followed for 12-months post-intervention. Participants in the intervention group (n=44) had a significantly greater hazard ratio of falls (2.01; 95% CI = 1.11 to 3.63) than the control group (n=45) when accounting for the history of falls, frailty status, cognition level, and sex. Conclusion: Participants who received a standing intervention over 22 weeks were twice as likely to fall 12 months after the intervention compared with the control group. However, the prevalence of falls did not surpass what would be typically observed in LTC facilities. It is imperative that future studies describe in detail the context in which falls happen and collect more characteristics of participants in the follow-up period to truly understand the association between standing more and the risk of falls.

Long-term care residents' acceptance of a standing intervention: A qualitative intrinsic case study.

Older adults in long-term care are sedentary. Standing is recommended to reduce sedentary time, but there is limited research on long-term care residents' acceptability of standing interventions. The acceptability of the Stand If You Can (SIYC) randomized clinical trial among long-term care residents was explored using a single intrinsic qualitative case study design. The five month intervention consisted of supervised 100 min standing sessions per week. Participants completed post-intervention interviews, which were analyzed using the Thematic Framework Analysis through the lens of an acceptability framework. The 10 participants (7 female), age 73 to 102 years, stood a median of 53% of the intervention offered time (range 20%-94%). The participants reported acceptability in many aspects of the Theoretical Framework of Acceptability. Standing is a simple intervention to decrease sedentary time and seems to be accepted among long-term care residents when burden is not perceived as too high.

Passive Remote Monitoring and Aging in Place: A Scoping Review.

Passive remote monitoring is a relatively new technology that may support older adults to age in place. However, current knowledge about the effectiveness of this technology in extending older adults' independence is lacking. Therefore, we conducted a scoping review of studies examining passive remote monitoring to systematically synthesize evidence about the technology's effectiveness as an intervention. Our initial search of Embase, CINAHL, PubMed, and Scopus databases identified 486 unique articles. Of these, 14 articles met our inclusion criteria. Results show that passive remote monitoring technologies are being used in innovative and diverse ways to support older adults aging in place and their caregivers. More high-quality research on this topic is needed.

Organoids capture tissue-specific innate lymphoid cell development in mice and humans.

Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, murine intestinal and pulmonary organoids are harnessed to demonstrate that the epithelial niche is sufficient to drive tissue-specific maturation of all innate lymphoid cell (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex human induced pluripotent stem cell (hiPSC)-based gut and lung organoid models are used to demonstrate that human epithelial cells recapitulate maturation of ILC from a stringent systemic human ILCP population, but only when the organoid-associated stromal cells are depleted. These systems offer versatile and reductionist models to dissect the impact of environmental and mucosal niche cues on ILC maturation. In the future, these could provide insight into how ILC activity and development might become dysregulated in chronic inflammatory diseases.

Stakeholder Perspectives on In-home Passive Remote Monitoring to Support Aging in Place in the Province of New Brunswick, Canada: Rapid Qualitative Investigation.

BACKGROUND: The province of New Brunswick (NB) has one of the oldest populations in Canada, providing an opportunity to develop and test innovative strategies to address the unique health challenges faced by older adults. Passive remote monitoring technology has the potential to support independent living among older adults. Limited research has examined the benefits of and barriers to the adoption of this technology among community-dwelling older adults. OBJECTIVE: This study aimed to explore perceptions of in-home passive remote monitoring technology designed to support aging in place from the perspective of older adults, their family or friend caregivers, social workers, and government decision-makers in the province of NB, Canada. METHODS: Between October 2018 and March 2020, a rapid qualitative investigation of 28 one-on-one interviews was conducted in person or via telephone. Participants included 2 home support services clients and 11 family or friend caregivers who had used passive remote monitoring technology in their homes; 8 social workers who had worked as case managers for home support services clients; and 7 individuals who were key government decision-makers in the adoption, policy development, and use of the technology in the province of NB. The interviews focused on the following topics: decision to adopt the passive remote monitoring system, barriers to adopting the passive remote monitoring system, benefits of the passive remote monitoring system, impact on client health outcomes, and privacy concerns. The interviews were audio recorded, transcribed, and analyzed by a team of 6 researchers. Data analysis was conducted using a rapid assessment process approach that included matrix analysis. RESULTS: Participants reported that the use of the remote monitoring system allowed older adults to live at home longer and provided caregiver relief. Stakeholders were invested in meeting the home support (home care) needs of older adults. However, when it came to the use of remote monitoring, there was a lack of consensus about which clients it was well-suited for and the role that social workers should play in informing clients and caregivers about the service (role ambiguity, gatekeeping, and perceived conflicts of interest). CONCLUSIONS: Our findings highlight many benefits and challenges of the adoption of passive remote monitoring for clients, their family or friend caregivers, and public provincial health and social services systems. Passive remote monitoring is a valuable tool that can provide support to older adults and their family or friend caregivers when it is a good fit with client needs. Further work is needed in NB to increase public and social workers' awareness of the service and its benefits.

Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells.

Complex co-cultures of organoids with immune cells provide a versatile tool for interrogating the bi-directional interactions that underpin the delicate balance of mucosal homeostasis. These 3D, multi-cellular systems offer a reductionist model for addressing multi-factorial diseases and resolving technical difficulties that arise when studying rare cell types such as tissue-resident innate lymphoid cells (ILCs). This article describes a murine system that combines small intestine organoids and small intestine lamina propria derived helper-like type-1 ILCs (ILC1s), which can be readily extended to other ILC or immune populations. ILCs are a tissue-resident population that is particularly enriched in the mucosa, where they promote homeostasis and rapidly respond to damage or infection. Organoid co-cultures with ILCs have already begun shedding light on new epithelial-immune signaling modules in the gut, revealing how different ILC subsets impact intestinal epithelial barrier integrity and regeneration. This protocol will enable further investigations into reciprocal interactions between epithelial and immune cells, which hold the potential to provide new insights into the mechanisms of mucosal homeostasis and inflammation.

Work Environment Characteristics and Emotional Intelligence as Correlates of Nurses' Compassion Satisfaction and Compassion Fatigue: A Cross-Sectional Survey Study.

This cross-sectional survey study examined the relationship between Canadian nurses' work environment characteristics, emotional intelligence, compassion fatigue and compassion satisfaction (n = 1271). Psychological demands, decision latitude, supervisor and coworker support, and emotional intelligence (EI) were significantly correlated with nurses' compassion satisfaction and compassion fatigue, except for two EI subscales. Furthermore, these relationships were stronger for compassion satisfaction than compassion fatigue, suggesting that they are influenced by different factors. Our results highlight the importance of creating reasonable psychological demands, empowering nurses to make decisions in their jobs, supportive relationships at work, and fostering the development of nurses' EI.

Sustained Post-Developmental T-Bet Expression Is Critical for the Maintenance of Type One Innate Lymphoid Cells In Vivo.

Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.

The role of oral bacteria in inflammatory bowel disease.

Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.

The Relationship between Mucins and Ulcerative Colitis: A Systematic Review.

Mucins are a family of glycosylated proteins which are the primary constituents of mucus and play a dynamic role in the regulation of the protective mucosal barriers throughout the human body. Ulcerative colitis (UC) is an Inflammatory Bowel Disease (IBD) characterised by continuous inflammation of the inner layer of the large intestine, and in this systematic review we analyse currently available data to determine whether alterations exist in mucin activity in the colonic mucosa of UC patients. Database searches were conducted to identify studies published between 1990 and 2020 that assess the role of mucins in cohorts of UC patients, where biopsy specimens were resected for analysis and control groups were included for comparison. 5497 articles were initially identified and of these 14 studies were systematically selected for analysis, a further 2 articles were identified through citation chaining. Therefore, 16 studies were critically reviewed. 13 of these studies assessed the role of MUC2 in UC and the majority of articles indicated that alterations in MUC2 structure or synthesis had an impact on the colonic mucosa, although conflicting results were presented regarding MUC2 expression. This review highlights the importance of further research to enhance our understanding of mucin regulation in UC and summarises data that may inform future studies.

MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.

ILC1 drive intestinal epithelial and matrix remodelling.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor ß1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

Exploring the Attendance and Potential Benefits of Reducing Sitting Time for Residents in a Canadian Long-Term Care Setting: A Pilot Study.

Background: This study aimed to assess the attendance to a novel intervention aiming to reduce sitting time in a long-term care facility and exploring the potential functional benefits. Methods: The intervention consisted of research staff visiting a resident to promote standing for 10-minute sessions, three times per day (morning, afternoon and evening), 4 days per week (Monday-Wednesday-Friday and Sunday) over 10 weeks. The main outcome was attendance. Functional outcomes included walking speed, power, and strength. Results: A total of 28 participants agree to participate and 24 completed the trial. The average attendance averaged four sessions per week and averaged 45 minutes of standing weekly out of 120 minutes offered. Attendance was highest during the morning session (p = .02) and weekdays (p < .01). There was a significant improvement in the 30-second chair stand test (p < .05). Conclusion: Although well accepted, the attendance was low. Based on the information gathered suggestions can be made to improve the intervention, attendance, and potential benefits of such intervention.

Physiotherapists' Experiences Using the Ekso Bionic Exoskeleton with Patients in a Neurological Rehabilitation Hospital: A Qualitative Study.

Use of bionic overground exoskeletons to assist with neurological rehabilitation is becoming increasingly prevalent and has important implications for physiotherapists and their patients. Yet, there is a paucity of research about the impact of integrating this technology on physiotherapists' work. The purpose of this study was to explore how the training and implementation of using the Ekso robotic exoskeleton with patients affects physiotherapists' work. An exploratory qualitative study of three physiotherapists working at a neurological rehabilitation centre in Eastern Canada was conducted using one-on-one semistructured interviews in July 2017. Audio recordings were transcribed verbatim, and data was coded and analyzed using thematic analysis. Six themes emerged from the data: developing organizational capacity; ethical use of technology; benefits of the equipment; challenges of the equipment; cognitive workload; and the technological environment. The results suggest that the adoption and integration of bionic exoskeletons into rehabilitation practice is not as simple as training physiotherapists and giving them the device. More research is needed to understand the increased cognitive demands of working with patients using technologically advanced exoskeletons within a dynamic, technology-rich healthcare environment, while managing patient expectations and ethical use.

Caring Near and Far by Connecting Community-Based Clients and Family Member/Friend Caregivers Using Passive Remote Monitoring: Protocol for a Pragmatic Randomized Controlled Trial.

BACKGROUND: Significant chronic disease challenges exist among older adults. However, most older adults want to remain at home even if their health conditions challenge their ability to live independently. Yet publicly funded home care resources are scarce, private home care is expensive, and family/friend caregivers have limited capacity. Many older adults with chronic illness would require institutional care without the support from family member/friend caregivers. This role raises the risk of physical health problems, stress, burnout, and depression. Passive remote monitoring (RM), the use of sensors that do not require any action by the individual for the system to work, may increase the older adult's ability to live independently while also providing support and peace of mind to both the client and the family member/friend caregiver. OBJECTIVE: This paper presents the protocol of a study conducted in two provinces in Canada to investigate the impact of RM along with usual home care (the intervention) versus usual home care alone (control) on older adults with complex care. The primary outcome for this study is the occurrence of and time to events such as trips to emergency, short-term admission to the hospital, terminal admission to the hospital awaiting admission to long-term care, and direct admission to long-term care. The secondary outcomes for this study are (1) health care costs, (2) client functional status and quality of life in the home, (3) family/friend caregiver stress, and (4) family/friend caregiver functional health status. METHODS: The design for this study is an unblinded pragmatic randomized controlled trial (PRCT) with two parallel arms in two geographic strata (Ontario and Nova Scotia). Quantitative and qualitative methodologies will be used to address the study objectives. This PRCT is conceptually informed by the principles of client-centered care and viewing the family as the client and aims at providing supported self-management. RESULTS: This study is supported by the Canadian Institutes for Health Research. A primary completion date is anticipated in fall 2022. CONCLUSIONS: Findings from this real-world rigorous randomized trial will support Canadian decision-makers, providers, and clients and their caregivers in assessing the health, well-being, and economic benefits and the social and technological challenges of integrating RM technologies to support older adults to stay in their home, including evaluating the impact on the burden of care experienced by family/friend caregivers. With an aging population, this technology may reduce institutionalization and promote safe and independent living for the elderly as long as possible. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 79884651; http://www.isrctn.com/ISRCTN79884651. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15027.

Predictors of new graduate nurses' health over the first 4 years of practice.

AIM: To examine predictors of Canadian new graduate nurses' health outcomes over 1 year. DESIGN: A time-lagged mail survey was conducted. METHOD: New graduate nurses across Canada (N = 406) responded to a mail survey at two time points: November 2012-March 2013 (Time 1) and May-July 2014 (Time 2). Multiple linear regression (mental and overall health) and logistic regression (post-traumatic stress disorder risk) analyses were conducted to assess the impact of Time 1 predictors on Time 2 health outcomes. RESULTS: Both situational and personal factors were significantly related to mental and overall health and post-traumatic stress disorder risk. Regression analysis identified that cynicism was a significant predictor of all three health outcomes, while occupational coping self-efficacy explained unique variance in mental health and work-life interference explained unique variance in post-traumatic stress disorder risk.

Bench to bedside: Current advances in regenerative medicine.

Regenerative medicine is a diverse and rapidly evolving field, employing core expertise from biologists, engineers, and clinicians. Recently the field has made significant progress towards regenerating or replacing tissues lost to age, disease or injury. Current strategies include transplantation of adult or pluripotent stem cells to replace tissue or support tissue healing. Promising approaches for the future of regenerative medicine include stimulating endogenous stem cells for in situ repair, transplantation of organoids to repair minor tissue injury, and the use of interspecies chimerism to produce functional metabolic organs for transplantation. In our review we focus on these emerging strategies, paying particular attention to their current and prospective translational impacts and challenges.