Explore the vast range of titles available.

Toxoplasma gondii is an orally acquired pathogen that induces strong IFN-γ based immunity conferring protection but that can also be the cause of immunopathology. The response in mice is driven in part by well-characterized MyD88-dependent signaling pathways. Here we focus on induction of less well understood immune responses that do not involve this Toll-like receptor (TLR)/IL-1 family receptor adaptor molecule, in particular as they occur in the intestinal mucosa. Using eYFP-IL-12p40 reporter mice on an MyD88 -/- background, we identified dendritic cells, macrophages, and neutrophils as cellular sources of MyD88-independent IL-12 after peroral T . gondii infection. Infection-induced IL-12 was lower in the absence of MyD88, but was still clearly above noninfected levels. Overall, this carried through to the IFN-γ response, which while generally decreased was still remarkably robust in the absence of MyD88. In the latter mice, IL-12 was strictly required to induce type I immunity. Type 1 and type 3 innate lymphoid cells (ILC), CD4 + T cells, and CD8 + T cells each contributed to the IFN-γ pool. We report that ILC3 were expanded in infected MyD88 -/- mice relative to their MyD88 +/+ counterparts, suggesting a compensatory response triggered by loss of MyD88. Furthermore, bacterial flagellin and Toxoplasma specific CD4 + T cell populations in the lamina propria expanded in response to infection in both WT and KO mice. Finally, we show that My88-independent IL-12 and T cell mediated IFN-γ production require the presence of the intestinal microbiota. Our results identify MyD88-independent intestinal immune pathways induced by T . gondii including myeloid cell derived IL-12 production, downstream type I immunity and IFN-γ production by ILC1, ILC3, and T lymphocytes. Collectively, our data reveal an underlying network of immune responses that do not involve signaling through MyD88.

The apicomplexan Toxoplasma gondii induces strong protective immunity dependent upon recognition by Toll-like receptors (TLR)11 and 12 operating in conjunction with MyD88 in the murine host. However, TLR11 and 12 proteins are not present in humans, inspiring us to investigate MyD88-independent pathways of resistance. Using bicistronic IL-12-YFP reporter mice on MyD88+/+ and MyD88-/- genetic backgrounds, we show that CD11c+MHCII+F4/80- dendritic cells, F4/80+ macrophages, and Ly6G+ neutrophils were the dominant cellular sources of IL-12 in both wild type and MyD88 deficient mice after parasite challenge. Parasite dense granule protein GRA24 induces p38 MAPK activation and subsequent IL-12 production in host macrophages. We show that Toxoplasma triggers an early and late p38 MAPK phosphorylation response in MyD88+/+ and MyD88-/- bone marrow-derived macrophages. Using the uracil auxotrophic Type I T. gondii strain cps1-1, we demonstrate that the late response does not require active parasite proliferation, but strictly depends upon GRA24. By i. p. inoculation with cps1-1 and cps1-1:Δgra24, we identified unique subsets of chemokines and cytokines that were up and downregulated by GRA24. Finally, we demonstrate that cps1-1 triggers a strong host-protective GRA24-dependent Th1 response in the absence of MyD88. Our data identify GRA24 as a major mediator of p38 MAPK activation, IL-12 induction and protective immunity that operates independently of the TLR/MyD88 cascade.

Background Telehealth services are rapidly expanding across the globe yet under-served populations, particularly people experiencing homelessness (PEH), are at risk of being further marginalised in society if focussed interventions to address telehealth access are not implemented. The aim of this rapid review was to report on the patient experience of PEH when accessing telehealth services. Secondary objectives of the review were to summarise both the patient and health service outcomes that were reported. Methods This rapid review identified peer reviewed literature that explored patient experiences of telehealth for people experiencing homelessness. Databases searched were MEDLINE, Embase, APA PsychINFO and CINAHL. Study characteristics were extracted and during the second-phase, two authors independently extracted data from each paper using a framework for evaluating telehealth outcomes (access to care, cost, experience, effectiveness) with a third author reviewing the extracted data and finalising the results table. Results Twelve eligible studies were identified with publication dates between 2020 and 2024. Two were qualitative, nine were quantitative and one was a mixed-methods study design. A large variation was found across the literature in relation to participant experience of telehealth for PEH. Telehealth was shown to be an acceptable form of healthcare for PEH. It was more acceptable in settings where participants were accessing it with clinician support, in an environment that was familiar to the participant, where the participant was living in at least temporary accommodation. Furthermore, telehealth was accessible where the processes to access telehealth were not prohibitive and where the internet connection was reliable. However, significant adaptions to improve a participant’s experience of telehealth was identified as a need. Conclusion There is limited evidence available that explores the experiences of PEH when accessing telehealth. We have identified a number of simple factors that can be implemented to make telehealth services more accessible for PEH. Acknowledging that telehealth services are an accepted form of healthcare delivery across the globe, future research involving people experiencing primary homelessness and undertaking research utilising a digital inclusion framework would be of value. Registration The review was registered on the International prospective register of systematic reviews, (PROSPERO in October 2023 CRD42023466817).

We evaluated two commonly used methods to estimate maximum metabolic rate (MMR) in fishes (measured via oxygen consumption rate). The ‘chase method’, where fish are chased to exhaustion and transferred to a chamber for post-exercise measurement of oxygen consumption rate, underestimated MMR by ~20% when compared against using a swim tunnel respirometer. The difference was consistent across body sizes, temperatures and two species—each of which has important implications when using these measurements to inform conservation planning.AbstractExperimental biologists now routinely quantify maximum metabolic rate (MMR) in fishes using respirometry, often with the goal of calculating aerobic scope and answering important ecological and evolutionary questions. Methods used for estimating MMR vary considerably, with the two most common methods being (i) the ‘chase method’, where fish are manually chased to exhaustion and immediately sealed into a respirometer for post-exercise measurement of oxygen consumption rate (ṀO2), and (ii) the ‘swim tunnel method’, whereby ṀO2 is measured while the fish swims at high speed in a swim tunnel respirometer. In this study, we compared estimates for MMR made using a 3-min exhaustive chase (followed by measurement of ṀO2 in a static respirometer) versus those made via maximal swimming in a swim tunnel respirometer. We made a total of 134 estimates of MMR using the two methods with juveniles of two salmonids (Atlantic salmon Salmo salar and Chinook salmon Oncorhynchus tshawytscha) across a 6°C temperature range. We found that the chase method underestimated ‘true’ MMR (based on the swim tunnel method) by ca. 20% in these species. The gap in MMR estimates between the two methods was not significantly affected by temperature (range of ca. 15–21°C) nor was it affected by body mass (overall range of 53.5–236 g). Our data support some previous studies that have suggested the use of a swim tunnel respirometer generates markedly higher estimates of MMR than does the chase method, at least for species in which a swim tunnel respirometer is viable (e.g. ‘athletic’ ram ventilating fishes). We recommend that the chase method could be used as a ‘proxy’ (i.e. with a correction factor) for MMR in future studies if supported by a species-specific calibration with a relevant range of temperatures, body sizes or other covariates of interest.

As a model infectious microbe and an important human pathogen, the apicomplexan Toxoplasma gondii has provided many important insights into innate and adaptive immunity to infection. We show here that a low virulence uracil auxotrophic Toxoplasma strain emerges as a virulent parasite in the absence of an intact T cell compartment. Both CD4 + and CD8 + T lymphocytes are required for optimal protection, in line with previous findings in other models of Toxoplasma infection. Nevertheless, several novel aspects of the response were identified in our study. Protection occurs independently of IL-12 and MyD88 and only partially requires IFN-γ. This is noteworthy particularly because the cytokines IL-12 and IFN-γ have previously been regarded as essential for protective immunity to T. gondii . Instead, we identified the anti-inflammatory effects of T cell-dependent IL-10 as the critical factor enabling host survival. The parasite dense granule protein GRA24, a host-directed mitogen-activated protein kinase activator, was identified as a major virulence factor in T cell-deficient hosts. Collectively, our results provide new and unexpected insights into host resistance to Toxoplasma .

Background Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. Methods A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman’s multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. Results Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America ( n  = 17), United Kingdom ( n  = 5), Australia ( n  = 5) and Canada ( n  = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of ‘accessible and timely’, ‘person-centred’, and values of ‘dignity and respect’ and ‘kindness with compassion’ were most prevalent. Among the three patient experience surveys identified, ‘accessible and timely’ and ‘person-centred’ were the most frequent domains. The least frequently highlighted domains and values were ‘equitable’ and ‘holistic’. No questions addressed the ‘safety’ domain. Conclusions The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of ‘Kindness and compassion’ require further emphasis when seeking feedback on healthcare experiences and the domains of ‘safety’, ‘equitable’, and ‘efficiency’ are not adequately represented in existing patient experience surveys.

ObjectivesTo determine the feasibility of conducting a multisite randomised controlled trial of the Healthy and HomED model of care to determine its capacity to reduce emergency department (ED) representations among people experiencing homelessness.DesignFeasibility randomised controlled trial with process evaluation.SettingSingle site public metropolitan ED.ParticipantsOur goal was to recruit 204 adults experiencing homelessness attending ED. In total, 190 participants were enrolled. The final sample comprised n=101 control and n=86 intervention.InterventionsThe Healthy and HomED model of care comprises screening for homelessness, assessing unmet needs via the Homeless Health Access to Care Tool and a Decision Assistance Guide that informs care planning. The intervention was applied by the Assessment Liaison Early Referral Team (ALERT), an ED-based multidisciplinary team specialised in supporting underserved populations.Main outcome measuresClinician acceptability of the implementation of the model of care, improved identification of homelessness and a reduction in ED representations within 28 days among people experiencing homelessness.ResultsImplementation of the Healthy and HomED model of care was feasible to the ALERT clinicians and the research team. While the Healthy and HomED did not significantly reduce representations to the ED, it improved the identification of homelessness by a third (35.3%). Qualitative findings suggest that the Homeless Health Access to Care Tool provided helpful standardisation to assessments. The Decision Assistance Guide was seldom added to the plan of care for senior clinicians but was reportedly helpful to junior clinicians with less experience in homeless healthcare.ConclusionsThe study provided assurance that running a multicentre hybrid trial to test the effectiveness and implementation of the Healthy and HomED is feasible. Process evaluation found that intervention adherence could be improved with greater contextualisation to local resources and increased engagement from ED medical and nursing teams. These factors could be addressed through the codesign of a future multisite trial.Trial registration numberANZCTR 12622001085763.

Toxoplasma gondii induces strong IFN-γ–based immunity. Innate lymphoid cells (ILC), in particular ILC1, are an important innate source of this protective cytokine during infection. Our objective was to determine how MyD88-dependent signaling influences ILC function during peroral compared with i.p. infection with T. gondii. MyD88+/+ and MyD88−/− mice were orally inoculated with ME49 cysts, and small intestinal lamina propria ILC were assessed using flow cytometry. We observed T-bet+ ILC1, retinoic acid–related orphan receptor γt+ ILC3, and a population of T-bet+retinoic acid–related orphan receptor γt+ double-positive ILC. In MyD88−/− mice, IFN-γ–producing T-bet+ ILC1 frequencies were reduced compared with wild-type. Treatment of MyD88−/− mice with an antibiotic mixture to deplete microflora reduced IFN-γ+ ILC1 frequencies. To examine ILC responses outside of the mucosal immune system, peritoneal exudate cells were collected from wild-type and knockout mice after i.p. inoculation with ME49 cysts. In this compartment, ILC were highly polarized to the ILC1 subset that increased significantly and became highly positive for IFN-γ over the course of infection. Increased ILC1 was associated with expression of the Ki67 cell proliferation marker, and the response was driven by IL-12p40. In the absence of MyD88, IFN-γ expression by ILC1 was not maintained, but proliferation remained normal. Collectively, these data reveal new aspects of ILC function that are influenced by location of infection and shaped further by MyD88-dependent signaling.

COVID-19 has spread rapidly around the world and taken over 2.6 million lives. Older adults experience disproportionate morbidity and mortality from the disease because increasing age and the presence of comorbidities are important predictors of negative outcomes. Lasting effects of COVID-19 have been described after recovery from the acute illness despite eradication of the virus from the body. The impact of COVID-19 on a person’s biological health post-infection is observed in multiple systems including respiratory, cardiac, renal, haematological, and neurological. Psychological dysfunction following recovery is also prevalent. Social factors such as distancing and stay at home measures leave older adults isolated and food insecure; they also face intertwined financial and health risks due to the resulting economic shutdown. This study examines the effects of COVID-19 on older adults using the biopsychosocial model framework.