Explore the vast range of titles available.

Periodontitis is an incredibly prevalent chronic inflammatory disease, which results in the destruction of tooth supporting structures. However, in addition to causing tooth and alveolar bone loss, this oral inflammatory disease has been shown to contribute to disease states and inflammatory pathology at sites distant from the oral cavity. Epidemiological and experimental studies have linked periodontitis to the development and/or exacerbation of a plethora of other chronic diseases ranging from rheumatoid arthritis to Alzheimer's disease. Such studies highlight how the inflammatory status of the oral cavity can have a profound impact on systemic health. In this review we discuss the disease states impacted by periodontitis and explore potential mechanisms whereby oral inflammation could promote loss of homeostasis at distant sites.

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consolidation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irreversible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI-dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology inmurine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ −/− mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis.

During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60 days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.

Following publication of this article, the authors noticed an error in the abstract, where they incorrectly stated that: “Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irreversible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI−/−-dependent fashion”. This has now been corrected to: “Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irreversible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI-dependent fashion”. The authors would like to apologise for this error. This has been corrected in both the PDF and HTML versions of the article.

Background An integral component of research within a learning health system is patient engagement at all stages of the research process. While there are well‐defined best practices for engaging with patients on predetermined research questions, there is little specific methodology for engaging patients at the stage of research question formation and prioritization. Further, with an emerging disease such as Long COVID, population‐specific strategies for meaningful engagement have not been characterized. Methods The COVID‐19 Focused Virtual Patient Engagement Studio (CoVIP studio) was a virtual panel created to facilitate patient‐centered studies surrounding the effects of long‐term COVID (“Long COVID”) also known as post‐acute SARS‐CoV‐2 syndrome (PASC). A diverse group of panelists was recruited and trained in several different areas of knowledge, competencies, and abilities regarding research and Long COVID. A three‐step approach was developed that consisted of recording panelists' broad wonderings to generate patient‐specific research questions. Results The “wonderings” discussed in panelists' training sessions were analyzed to identify specific populations, interventions, comparators, outcomes, and timeframes (PICOT) elements, which were then used to create a survey to identify the elements of greatest importance to the panel. Based on the findings, 10 research questions were formulated using the PICOT format. The panelists then ranked the questions on perceived order of importance and distributed one million fictional grant dollars between the five chosen questions in the second survey. Through this stepwise prioritization process, the project team successfully translated panelists' research wonderings into investigable research questions. Conclusion This methodology has implications for the advancement of patient‐engaged prioritization both within the scope of Long COVID research and in research on other rare or emerging diseases.

Periodontitis is a prevalent chronic inflammatory disease that involves the destruction of the supporting structures of the teeth. In addition to local tissue damage and bone loss, periodontitis has been shown to have adverse consequences at sites distant from the oral cavity. Growing epidemiological and experimental data has associated periodontitis with the development and/or exacerbation of a myriad of clinically-important diseases, from rheumatoid arthritis to Alzheimer's disease to ischaemic stroke. The objective of this thesis was to provide an insight into the local and systemic immune responses during experimental periodontitis which could potentially affect peripheral tissue sites, with a particular focus on the impact on stroke severity.Using an acute bilateral ligature model in mice, we found that experimental periodontitis led to bone loss, bacterial growth, and increased local inflammatory cell mobilisation. Systemically, periodontitis altered the frequencies of monocytes and neutrophils in the bone marrow and small intestine, increased circulating levels of the pro-inflammatory cytokines, interleukin (IL)-1β and IL-17A, and increased tumour necrosis factor (TNF)α production in bone marrow monocytes.In order to evaluate the impact of periodontitis on stroke outcome, we applied this ligature-induced model and induced experimental strokes by transient or permanent occlusion of the middle cerebral artery. In tandem with ligature placement, we systemically challenged with an oral-specific lipopolysaccharide (LPS) in an effort to imitate the systemic aspects of the clinical disease. However, periodontitis alone or in tandem with LPS, did not alter systemic immune trafficking, blood-brain barrier disruption, or brain damage after stroke.In addition to the systemic reaches of periodontitis, we also focused on local immune regulation during disease. In this way, we identified the gingiva as a novel site of extramedullary haematopoiesis that harbours a population of haematopoietic stem and progenitor cells in the tissue which can give rise to multiple lineages of myeloid immune cells, including tissue monocytes. We also describe that these stem cells are differentially modulated by induced or natural bone loss and provide evidence that stromal cells and the surrounding matrix may be important in retaining these progenitors in the gingival niche.Overall, these findings give insight into the fundamental immunological mechanisms during periodontitis, both in a local context, within the oral cavity, as well as the implications at distant tissues sites. We specifically provide evidence that periodontitis does not alter outcome after acute ischaemic stroke, and thus add an important counterpoint to the growing body of literature associating periodontitis with a negative impact on stroke.

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Acute episodes of delirium also contribute significantly to rates of long-term cognitive decline, implying that de novo pathology occurs during these acute episodes. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms has not been investigated. Here we show that systemic inflammation, induced by bacterial LPS, produces both working memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 g/kg) did not affect working memory but robustly impaired contextual fear conditioning (CFC). However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1 beta; replicated, these working memory deficits. Although LPS-induced deficits still occured in IL-1RI-/- mice, systemic TNF-alpha; was sufficient to induce similar deficits, indicating redundancy among these cytokines. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits despite failing to block brain IL-1 beta; synthesis. Direct application of IL-1 beta; to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI-/- dependent-fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1 beta; but dysfunction leading to neuronal death is mediated by hippocampal IL-1 beta;. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury that may lead to long-term cognitive impairment but that these events are mechanistically dissociable. This would have significant implications for management of cognitive dysfunction and decline during acute illness.

In December 2018, the Danish Meteorological Institute organised an international meeting on the subject of crowdsourced data in numerical weather prediction (NWP) and weather forecasting. The meeting, spanning 2 days, gathered experts on crowdsourced data from both meteorological institutes and universities from Europe and the United States. Scientific presentations highlighted a vast array of possibilities and progress being made globally. Subjects include data from vehicles, smartphones, and private weather stations. Two groups were created to discuss open questions regarding the collection and use of crowdsourced data from different observing platforms. Common challenges were identified and potential solutions were discussed. While most of the work presented was preliminary, the results shared suggested that crowdsourced observations have the potential to enhance NWP. A common platform for sharing expertise, data, and results would help crowdsourced data realise this potential. In December 2018, the Danish Meteorological Institute organised an international meeting on the subject of crowdsourced data in numerical weather prediction (NWP) and weather forecasting. The meeting, spanning 2 days, gathered experts on crowdsourced data from both meteorological institutes and universities from Europe and the United States. It was concluded that crowdsourced observations are likely to be useful for NWP. Finally, it is recommended that a platform for sharing thoughts, data and results is worked upon moving forward.