The gut-brain and gut-macrophage contribution to gastrointestinal dysfunction with systemic inflammation.

The gastrointestinal tract is one of the main organs affected during systemic inflammation and disrupted gastrointestinal motility is a major clinical manifestation. Many studies have investigated the involvement of neuroimmune interactions in regulating colonic motility during localized colonic inflammation, i.e., colitis. However, little is known about how the enteric nervous system and intestinal macrophages contribute to dysregulated motility during systemic inflammation. Given that systemic inflammation commonly results from the innate immune response against bacterial infection, we mimicked bacterial infection by administering lipopolysaccharide (LPS) to rats and assessed colonic motility using ex vivo video imaging techniques. We utilized the Cx3cr1-Dtr rat model of transient depletion of macrophages to investigate the role of intestinal macrophages in regulating colonic motility during LPS infection. To investigate the role of inhibitory enteric neurotransmission on colonic motility following LPS, we applied the nitric oxide synthase inhibitor, Nω-nitro-L-arginine (NOLA). Our results confirmed an increase in colonic contraction frequency during LPS-induced systemic inflammation. However, neither the depletion of intestinal macrophages, nor the suppression of inhibitory enteric nervous system activity impacted colonic motility disruption during inflammation. This implies that the interplay between the enteric nervous system and intestinal macrophages is nuanced, and complex, and further investigation is needed to clarify their joint roles in colonic motility.

Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages.

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1ß secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1ß, IL-6 and TNF-α from LPS-primed rodent macrophages using the J774 mouse macrophage cell line and primary rat peritoneal macrophages. We compared the immediate P2X7 responses in un-primed and LPS-primed macrophages and found no difference in calcium response amplitude or kinetics. These results suggest that under inflammatory conditions positive allosteric modulators are capable of increasing cytokine secretion at lower concentrations of ATP, thus boosting the initial pro-inflammatory signal. This may be important in the control of intracellular infections.

"Family doctors are also people": a qualitative analysis of how family physicians managed competing personal and professional responsibilities during the COVID-19 pandemic.

BACKGROUND: Family physicians (FPs) fill an essential role in public health emergencies yet have frequently been neglected in pandemic response plans. This exclusion harms FPs in their clinical roles and has unintended consequences in the management of concurrent personal responsibilities, many of which were amplified by the pandemic. The objective of our study was to explore the experiences of FPs during the first year of the COVID-19 pandemic to better understand how they managed their competing professional and personal priorities. METHODS: We conducted semi-structured interviews with FPs from four Canadian regions between October 2020 and June 2021. Employing a maximum variation sampling approach, we recruited participants until we achieved saturation. Interviews explored FPs' personal and professional roles and responsibilities during the pandemic, the facilitators and barriers that they encountered, and any gender-related experiences. Transcribed interviews were thematically analysed. RESULTS: We interviewed 68 FPs during the pandemic and identified four overarching themes in participants' discussion of their personal experiences: personal caregiving responsibilities, COVID-19 risk navigation to protect family members, personal health concerns, and available and desired personal supports for FPs to manage their competing responsibilities. While FPs expressed a variety of ways in which their personal experiences made their professional responsibilities more complicated, rarely did that affect the extent to which they participated in the pandemic response. CONCLUSIONS: For FPs to contribute fully to a pandemic response, they must be factored into pandemic plans. Failure to appreciate their unique role and circumstances often leaves FPs feeling unsupported in both their professional and personal lives. Comprehensive planning in anticipation of future pandemics must consider FPs' varied responsibilities, health concerns, and necessary precautions. Having adequate personal and practice supports in place will facilitate the essential role of FPs in responding to a pandemic crisis while continuing to support their patients' primary care needs.

The role of microglia and monocytes in the generation and resolution of the immune response in female and male rats.

Microglia have long been thought to be responsible for the initiation of the central nervous system (CNS) immune response to pathogen exposure. However, we recently reported that depleting CNS microglia and circulating monocytes does not abrogate the sickness response in male rats or mice to bacterial endotoxin, lipopolysaccharide (LPS). How the central immune response to an endotoxin challenge is initiated and resolved in the absence of microglia and monocytes remains unclear. Here we investigated the role of microglia and monocytes in driving the behavioral, febrile and neuroimmune response to LPS using the Cx3cr1-Dtr rat model of conditional microglia/monocyte depletion, assessed if this role is similar in females and males, and examined how the response to an immune challenge might be initiated in the absence of these cells. We show that depletion of microglia and monocytes exacerbates the response to LPS at each phase of the immune cascade. Our data indicate that the changes in the central response to immune challenge may be an indirect effect of excess neutrophil expansion into the bloodstream and infiltration into peripheral organs stimulating a rapid and exacerbated cytokine and prostaglandin response to the LPS that is not curtailed by the usual negative feedback mechanisms. Thus, we show that a demonstrable immune response can be generated (and resolved) in the near complete absence of microglia and monocytes and that these cells play a regulatory role in the initiation and resolution of the response to an immune challenge, rather than being critical for it to occur.

The prevalence of self-reported mental illness among those imprisoned in New South Wales across three health surveys, from 2001 to 2015.

OBJECTIVE: The prevalence of mental illness among those in prison is much higher than in the community; however, very few studies have examined whether rates have changed over time, in line with increasing self-reported rates in the community. METHODS: This study compares the prevalence of self-reported mental illness, self-harm and suicidal thoughts/behaviours, and drug and alcohol use across three waves (2001, 2009 and 2015) of health surveys involving men and women in New South Wales prisons and compared these rates with published community-level findings. RESULTS: The prevalence of those reporting any mental health diagnosis increased significantly across the three surveys, even after adjustment for socio-demographic and criminal justice variables that also changed over time. Individuals surveyed in 2015 were more likely to report a mental health diagnosis than those surveyed in 2001 (adjusted odds ratio = 2.66, 95% confidence interval = [2.16, 3.27]). The prevalence of self-harm and suicidal thoughts and behaviours remained stable across the three surveys, while self-reported regular drug use decreased over the period. Women experienced a far greater burden of mental illness than men across all three surveys and experienced more growth in the prevalence of most psychiatric disorders. CONCLUSION: These findings have important implications for public and prison health systems given the poor social, health and criminal justice outcomes of those imprisoned with mental illness, both in custody and post-release.

"There's nothing like a good crisis for innovation": a qualitative study of family physicians' experiences with virtual care during the COVID-19 pandemic.

BACKGROUND: Prior to the pandemic, Canada lagged behind other Organisation for Economic Cooperation and Development countries in the uptake of virtual care. The onset of COVID-19, however, resulted in a near-universal shift to virtual primary care to minimise exposure risks. As jurisdictions enter a pandemic recovery phase, the balance between virtual and in-person visits is reverting, though it is unlikely to return to pre-pandemic levels. Our objective was to explore Canadian family physicians' perspectives on the rapid move to virtual care during the COVID-19 pandemic, to inform both future pandemic planning for primary care and the optimal integration of virtual care into the broader primary care context beyond the pandemic. METHODS: We conducted semi-structured interviews with 68 family physicians from four regions in Canada between October 2020 and June 2021. We used a purposeful, maximum variation sampling approach, continuing recruitment in each region until we reached saturation. Interviews with family physicians explored their roles and experiences during the pandemic, and the facilitators and barriers they encountered in continuing to support their patients through the pandemic. Interviews were audio-recorded, transcribed, and thematically analysed for recurrent themes. RESULTS: We identified three prominent themes throughout participants' reflections on implementing virtual care: implementation and evolution of virtual modalities during the pandemic; facilitators and barriers to implementing virtual care; and virtual care in the future. While some family physicians had prior experience conducting remote assessments, most had to implement and adapt to virtual care abruptly as provinces limited in-person visits to essential and urgent care. As the pandemic progressed, initial forays into video-based consultations were frequently replaced by phone-based visits, while physicians also rebalanced the ratio of virtual to in-person visits. Medical record systems with integrated capacity for virtual visits, billing codes, supportive clinic teams, and longitudinal relationships with patients were facilitators in this rapid transition for family physicians, while the absence of these factors often posed barriers. CONCLUSION: Despite varied experiences and preferences related to virtual primary care, physicians felt that virtual visits should continue to be available beyond the pandemic but require clearer regulation and guidelines for its appropriate future use.

Decoloniality and healthcare higher education: Critical conversations.

BACKGROUND: We explore the theoretical and methodological aspects of decolonising speech and language therapy (SLT) higher education in the United Kingdom. We begin by providing the background of the Rhodes Must Fall decolonisation movement and the engagement of South African SLTs in the decoloniality agenda. We then discuss the evolution of decoloniality in SLT, highlighting its focus on reimagining the relationships between participants, students, patients and the broader world. OBJECTIVE: The primary objective of this discussion is to fill a gap in professional literature regarding decoloniality in SLT education. While there is limited research in professional journals, social media platforms have witnessed discussions on decolonisation in SLT. This discussion aims to critically examine issues such as institutional racism, lack of belonging, inequitable services and limited diversity that currently affect the SLT profession, not just in the United Kingdom but globally. METHODS: The methods employed in this research involve the engagement of SLT academics in Critical conversations on decolonisation. These conversations draw on reflexivity and reflexive interpretation, allowing for a deeper understanding of the relationship between truth, reality, and the participants in SLT practice and education. The nature of these critical conversations is characterised by their chaotic, unscripted and fluid nature, which encourages the open discussion of sensitive topics related to race, gender, class and sexuality. DISCUSSION POINTS: We present our reflections as academics who participated in the critical conversations. We explore the discomfort experienced by an academic when engaging with decolonisation, acknowledging white privilege, and the need to address fear and an imposter syndrome. The second reflection focuses on the experiences of white academics in grappling with their complicity in a system that perpetuates racism and inequality. It highlights the need for self-reflection, acknowledging white privilege and working collaboratively with colleagues and students toward constructing a decolonised curriculum. Finally, we emphasise that while action is crucial, this should not undermine the potential of dialogue to change attitudes and pave the way for practical implementation. The paper concludes by emphasising the importance of combining dialogue with action and the need for a nuanced understanding of the complexities involved in decolonising SLT education. CONCLUSION: Overall, this paper provides a comprehensive overview of the background, objectives, methods and key reflections related to the decolonisation of SLT higher education in the United Kingdom. It highlights the challenges, discomfort and responsibilities faced by academics in addressing decoloniality and emphasizes the importance of ongoing critical conversations and collective action in effecting meaningful change. WHAT THIS PAPER ADDS: What is already known on this subject Prior to this paper, it was known that the decolonial turn in speech and language therapy (SLT) was a recent focus, building on a history of professional transformation in South Africa. However, there was limited literature on decoloniality in professional journals, with most discussions happening on social media platforms. This paper aims to contribute to the literature and provide a critical conversation on decolonising SLT education, via the United Kingdom. What this paper adds to existing knowledge This paper adds a critical conversation on decolonising SLT higher education. It explores theoretical and methodological aspects of decoloniality in the profession, addressing issues such as institutional racism, lack of sense of belonging, inequitable services and limited diversity. The paper highlights the discomfort experienced by academics in engaging with decolonisation and emphasizes the importance of reflection, collaboration and open dialogue for meaningful change. Notably we foreground deimperialisation (vs. decolonisation) as necessary for academics oriented in/with the Global North so that both processes enable each other. Deimperialisation is work that focuses the undoing of privilege exercised by academics in/with the Global North not only for localising their research and education agenda but checking their rite of passage into the lives of those in the Majority World. What are the potential or actual clinical implications of this work? The paper highlights the need for SLT practitioners and educators to critically examine their practices and curricula to ensure they are inclusive, decolonised and responsive to the diverse needs of communities. The discussions emphasise the importance of addressing institutional racism and promoting a sense of belonging for research participants, SLT students and patients. This paper offers insights and recommendations that can inform the development of more equitable and culturally responsive SLT services and education programmes.

Disparities in access to primary care are growing wider in Canada.

Canadian provinces and territories have undertaken varied reforms to how primary care is funded, organized, and delivered, but equity impacts of reforms are unclear. We explore disparities in access to primary care by income, educational attainment, dwelling ownership, immigration, racialization, place of residence (metropolitan/non-metropolitan), and sex/gender, and how these have changed over time, using data from the Canadian Community Health Survey (2007/08 and 2015/16 or 2017/18). We observe disparities by income, educational attainment, dwelling ownership, recent immigration, immigration (regular place of care), racialization (regular place of care), and sex/gender. Disparities are persistent over time or increasing in the case of income and racialization (regular medical provider and consulted with a medical professional). Primary care policy decisions that do not explicitly consider existing inequities may continue to entrench them. Careful study of equity impacts of ongoing policy reforms is needed.

An analysis of policies supporting the roles of family physicians in four regions in Canada during the COVID-19 pandemic.

Policy supports are needed to ensure that Family Physicians (FPs) can carry out pandemic-related roles. We conducted a document analysis in four regions in Canada to identify regulation, expenditure, and public ownership policies during the COVID-19 pandemic to support FP pandemic roles. Policies supported FP roles in five areas: FP leadership, Infection Prevention and Control (IPAC), provision of primary care services, COVID-19 vaccination, and redeployment. Public ownership polices were used to operate assessment, testing and vaccination, and influenza-like illness clinics and facilitate access to personal protective equipment. Expenditure policies were used to remunerate FPs for virtual care and carrying out COVID-19-related tasks. Regulatory policies were region-specific and used to enact and facilitate virtual care, build surge capacity, and enforce IPAC requirements. By matching FP roles to policy supports, the findings highlight different policy approaches for FPs in carrying out pandemic roles and will help to inform future pandemic preparedness.

The roles of family physicians during a pandemic.

Family physicians play important roles throughout all stages of a pandemic response; however, actionable descriptions outlining these roles are absent from current pandemic plans. Using a multiple case study design, we conducted a document analysis and interviewed 68 family physicians in four Canadian regions. We identified roles performed by family physicians in five distinct stages of pandemic response: pre-pandemic, phased closure and re-opening, acute care crisis, vaccination, and pandemic recovery. In addition to adopting public health guidance to ensure continued access to primary care services, family physicians were often expected to operationalize public health roles (eg, staffing assessment centres), modulate access to secondary/tertiary services, help provide surge capacity in acute care facilities, and enhance supports and outreach to vulnerable populations. Future pandemic plans should include family physicians in planning, explicitly incorporate family physician roles, and ensure needed resources are available to allow for an effective primary care response.

Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses.

Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms. Exercise training appears to maintain telomeres in certain somatic cells, although the underlying molecular mechanisms are incompletely understood. Here, we examined the influence of a single bout of vigorous exercise training on leukocyte telomerase reverse transcriptase (TERT) and shelterin gene expression, and the abundance of three microRNAs (miRNAs) implicated in biological ageing (miRNA-143, -223 and -486-5p) in an elite athlete and large animal model, Thoroughbred horses. Gene and miRNA expression were analysed using primer-based and TaqMan Assay qPCR. Leukocyte TRF1, TRF2 and POT1 expression were all significantly increased whilst miR-223 and miR-486-5p were decreased immediately after vigorous exercise (all p < 0.05), and tended to return to baseline levels 24 h after training. Relative to the young horses (~ 3.9 years old), middle-aged horses (~ 14.8 years old) exhibited reduced leukocyte TERT gene expression, and increased POT1 and miR-223 abundance (all p < 0.05). These data demonstrate that genes transcribing key components of the shelterin-telomere complex are influenced by ageing and dynamically regulated by a single bout of vigorous exercise in a large, athletic mammal - Thoroughbred horses. Our findings also implicate TERT and shelterin gene transcripts as potential targets of miR-223 and miR-486-5p, which are modulated by exercise and may have a role in the telomere maintenance and genomic stability associated with long-term aerobic training.

Examining enteric nervous system function in rat and mouse: an interspecies comparison of colonic motility.

Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and postoperative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study provides a comparison of colonic motility in the mouse and rat to clarify species differences and assess the relative effectiveness of each animal model for colonic motility research. We describe the protocol modifications and optimization undertaken to enable video imaging of colonic motility in the rat. Apart from the broad difference in terms of gastrointestinal diameter and length, we identified differences in the fundamental histology of the proximal colon such that the rat had larger villus height-to-width and villus height-to-crypt depth ratios compared with mouse. Since gut motility is tightly regulated by the enteric nervous system (ENS), we investigated how colonic contractile activity within each rodent species responds to modulation of the ENS inhibitory neuronal network. Here we used Nω-nitro-l-arginine (l-NNA), an inhibitor of nitric oxide synthase (NOS) to assess proximal colon responses to the stimulatory effect of blocking the major inhibitory neurotransmitter, nitric oxide (NO). In rats, the frequency of proximal colonic contractions increased in the presence of l-NNA (vs. control levels) to a greater extent than in mice. This is despite a similar number of NOS-expressing neurons in the myenteric plexus across species. Given this increase in colonic contraction frequency, the rat represents another relevant animal model for investigating how gastrointestinal motility is regulated by the inhibitory neuronal network of the ENS.NEW & NOTEWORTHY Mice and rats are widely used in gastrointestinal research but have fundamental differences that make them important as different models for different questions. We found that mice have a higher villi length-to-width and villi length-to-crypt depth ratio than rat in proximal colon. Using the ex vivo video imaging technique, we observed that rat colon has more prominent response to blockade of major inhibitory neurotransmitter (nitric oxide) in myenteric plexus than mouse colon.

Microglial ablation in rats disrupts the circadian system.

Microglia, the key neuroimmune cells of the central nervous system, are best known for their function in defending an individual from pathogens and injury. Recent findings, including our own, suggest microglia also have several immune-independent roles, including in regulating satiety, promoting memory, and modifying pain responses. Many of these microglia-associated functions are affected by circadian rhythmicity, thus, varying substantially depending upon the time of day. To gain further insight into this link, we used a Cx3cr1-Dtr transgenic Wistar rat model to acutely deplete microglia and examined if this could lead to a disruption in diurnal temperature, metabolism, and activity measures. We also examined if differences in the physiological rhythms corresponded with changes in the expression of key circadian rhythm-regulating genes and proteins. Our data show that in the absence of microglia there is a pronounced disruption of diurnal rhythms in several domains consistent with a shift toward the inactive phase, in conjunction with changes in circadian rhythm-regulating genes and proteins. These data suggest microglia are involved in the regulation of circadian rhythms and indicate an exciting potential to manipulate these cells to improve disrupted circadian rhythms such as with shift-work or jet-lag.

Family physicians' perspectives on the impact of COVID-19 on preventative care in primary care: findings from a qualitative study.

INTRODUCTION: Health system disruptions, caused by unexpected emergencies such as disease outbreaks, natural disasters, and cybercrimes, impact the delivery of routine preventative care. As comprehensive care providers, family physicians (FPs) devote significant time to prevention. However, without emergency and pandemic plans in place in primary care, FPs face added barriers to prioritizing and sustaining preventative care when health systems are strained, which was evident during the COVID-19 pandemic. This study aims to describe FPs' experiences providing preventative care during the COVID-19 pandemic and their perceptions of the impacts of disrupted preventative care in primary care settings. METHODS: Using a qualitative descriptive approach, we conducted semistructured interviews with FPs across 4 provinces in Canada (i.e. Newfoundland and Labrador, Nova Scotia, Ontario, British Columbia) between October 2020 and June 2021 as part of a larger multiple case study. These interviews broadly explored the roles and responsibilities of FPs during the COVID-19 pandemic. Interviews were coded thematically and codes from the larger study were analysed further using an iterative, phased process of thematic analysis. RESULTS: Interviews averaged 58 min in length (range 17-97 min) and FPs had a mean of 16.9 years of experience. We identified 4 major themes from interviews with FPs (n = 68): (i) lack of capacity and coordination across health systems, (ii) patient fear, (iii) impacts on patient care, and (iv) negative impacts on FPs. Physicians voiced concerns with managing patients' prevention needs when testing availability and coordination of services was limited. Early in the pandemic, patients were also missing or postponing their own primary care appointments. Change in the provision and coordination of routine preventative care had negative impacts on both patients and physicians, affecting disease incidence/progression, physician workload, and psychological wellbeing. CONCLUSION: During the COVID-19 pandemic, upstream care efforts were impacted, and FPs were forced to reduce their provision of preventative care. FPs contribute direct insight to primary care delivery that can support pandemic planning to ensure preventative care is sustained during future emergencies.

Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.

BACKGROUND: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly. METHODS: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013-2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients. RESULTS: Trivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45-59) for IIV4 versus 45% (95% CI, 34-54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency. CONCLUSIONS: The uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized Open-Label Trial.

BACKGROUND: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. METHODS: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. RESULTS: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. CONCLUSIONS: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4. CLINICAL TRIALS REGISTRATION: NCT03722589.

Ovarian follicles are resistant to monocyte perturbations-implications for ovarian health with immune disruption†.

Monocytes and macrophages are the most abundant immune cell populations in the adult ovary, with well-known roles in ovulation and corpus luteum formation and regression. They are activated and proliferate in response to immune challenge and are suppressed by anti-inflammatory treatments. It is also likely they have a functional role in the healthy ovary in supporting the maturing follicle from the primordial through to the later stages; however, this role has been unexplored until now. Here, we utilized a Cx3cr1-Dtr transgenic Wistar rat model that allows a conditional depletion of circulating monocytes, to investigate their role in ovarian follicle health. Our findings show that circulating monocyte depletion leads to a significant depletion of ovarian monocytes and monocyte-derived macrophages. Depletion of monocytes was associated with a transient reduction in circulating anti-Müllerian hormone (AMH) at 5 days postdepletion. However, the 50-60% ovarian monocyte/macrophage depletion had no effect on ovarian follicle numbers, follicle atresia, or apoptosis, within 5-21 days postdepletion. These data reveal that the healthy adult ovary is remarkably resistant to perturbations of circulating and ovarian monocytes despite acute changes in AMH. These data suggest that short-term anti-inflammatory therapies that transiently impact on circulating monocytes are unlikely to disrupt ovarian follicle health, findings that have significant implications for fertility planning relative to the experience of an immune challenge or immunosuppression.

Maternal diet before and during pregnancy modulates microglial activation and neurogenesis in the postpartum rat brain.

The implications of poor maternal diet on offspring metabolic and neuroimmune development are well established. Increasing evidence now suggests that maternal obesity and poor diet can also increase the risk of postpartum mood disorders, but the mechanisms are unknown. Here we investigated the effects of a poor, high-fat-high-sugar diet (HFSD) on peripheral and central inflammation, neurogenesis and postpartum anxiety-like behaviours. We hypothesised that long-term consumption of a HFSD pre- and post-conception would increase the levels of circulating cytokines and induce microglial activation, particularly in the arcuate nucleus of the hypothalamus (ARC), as the primary brain region involved in the integration of satiety signalling; and this would lead to increased anxiety, stress responsivity and disrupted neurogenesis. We further hypothesised that these effects would be ameliorated by consumption of a healthier diet during pregnancy - specifically a diet high in omega-3 polyunsaturated fatty acids (PUFAs). As expected, the HFSD significantly increased pre-conception body weight, elevated circulating cytokines and activated microglia in the ARC, as well as in the basolateral amygdala. The HFSD also significantly increased the numbers of immature (doublecortin (DCX)-positive) neurons in the subgranular/granular region of the hippocampus, a neurogenic response that was, surprisingly, mimicked by consumption of a diet high in omega-3 PUFAs. Despite these effects of peri-pregnancy dietary imbalance, we detected no differences in anxiety-like behaviours or hypothalamic-pituitary-adrenal (HPA) axis reactivity between the groups. A shift to a healthier diet post-conception reversed the peripheral inflammation and alleviated the microglial activation. These novel data indicate the importance of a balanced peri-pregnancy diet and highlight the need for future research into key triggers that alter the neuroimmune balance in the maternal brain.

An Environmental Scan of Virtual "Walk-In" Clinics in Canada: Comparative Study.

BACKGROUND: Canada has been slow to implement virtual care relative to other countries. However, in recent years, the availability of on-demand, "walk-in" virtual clinics has increased, with the COVID-19 pandemic contributing to the increased demand and provision of virtual care nationwide. Although virtual care facilitates access to physicians while maintaining physical distancing, there are concerns regarding the continuity and quality of care as well as equitable access. There is a paucity of research documenting the availability of virtual care in Canada, thus hampering the efforts to evaluate the impacts of its relatively rapid emergence on the broader health care system and on individual health. OBJECTIVE: We conducted a national environmental scan to determine the availability and scope of virtual walk-in clinics, cataloging the services they offer and whether they are operating through public or private payment. METHODS: We developed a power term and implemented a structured Google search to identify relevant clinics. From each clinic meeting our inclusion criteria, we abstracted data on the payment model, region of operation, services offered, and continuity of care. We compared clinics operating under different payment models using Fisher exact tests. RESULTS: We identified 18 virtual walk-in clinics. Of the 18 clinics, 10 (56%) provided some services under provincial public insurance, although 44% (8/18) operated on a fully private payment model while an additional 39% (7/18) charged patients out of pocket for some services. The most common supplemental services offered included dermatology (15/18, 83%), mental health services (14/18, 78%), and sexual health (11/18, 61%). Continuity, information sharing, or communication with the consumers' existing primary care providers were mentioned by 22% (4/18) of the clinics. CONCLUSIONS: Virtual walk-in clinics have proliferated; however, concerns about equitable access, continuity of care, and diversion of physician workforce within these models highlight the importance of supporting virtual care options within the context of longitudinal primary care. More research is needed to support quality virtual care and understand its effects on patient and provider experiences and the overall health system utilization and costs.

Emerging roles of extracellular vesicles in the intercellular communication for exercise-induced adaptations.

Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary intercellular communication occurs partly through their paracrine and endocrine actions. Extracellular vesicles are nanoscale lipid membranes (30-2,000 nm in diameter) that shuttle functional biological material between cells. They are released from numerous tissues and are isolated from nearly all biofluids and cell cultures. Although their biogenesis, cell targeting, and functional roles are incompletely understood, they appear to have crucial roles in physiological and disease processes. Their enormous potential to serve as sensitive biomarkers of disease and also new therapeutic interventions for diseases have gained them considerable attention in recent years. Regular physical exercise training confers systemic health benefits and consequently prevents many age-related degenerative diseases. Many of the molecular mechanisms responsible for the salubrious effects of exercise are known, yet a common underlying mechanism potentially responsible for the holistic health benefits of exercise has only recently been explored (i.e., via extracellular vesicle transport of biological material). Here, we provide an overview of extracellular vesicle biology before outlining the current evidence on the capacity for a single bout and chronic exercise to elicit changes in extracellular vesicle content and modulate their molecular cargo (e.g., small RNAs). We highlight areas for future research and emphasize their potential utility as biomarkers and therapeutic strategies of disease and its prevention.