Mesenteric lymph nodes at the center of immune anatomy

The surface of the intestinal mucosa is constantly assaulted by food antigens and enormous numbers of commensal microbes and their products, which are sampled by dendritic cells (DCs). Recent work shows that the mesenteric lymph nodes (MLNs) are the key site for tolerance induction to food proteins and that they also act as a firewall to prevent live commensal intestinal bacteria from penetrating the systemic immune system

A protocol for a systematic review of clinical guidelines and published systematic reviews on the early detection of oral cancer

Background: The predicted increase in incidence of oral cavity cancer (OCC) coupled with high mortality and poor prognosis – particularly when diagnosed at a late/advanced stage – highlights the need for prevention and early detection/screening to reverse these trends. Dental healthcare professionals in primary care settings have a pivotal role in this effort. Aim: The aim of this protocol is to detail the process for assessing the evidence for the best practice and methods of early detection/screening for OCC in primary care dental settings by undertaking a systematic review of global clinical guidelines and published systematic reviews. Method: Searches for clinical guidelines and systematic reviews will be conducted in the following databases: Cochrane library, Medical Literature Analysis and Retrieval System Online (Ovid), Excerpta Medical dataBASE, PubMed, Turning Research into Practice, SCOPUS and Web of Science Core Collection. Our search will extend to include Google Scholar and international professional organizations/associations websites. In addition, we will handsearch the bibliographies and undertake citation searches of the selected papers. Quality appraisal will be undertaken using the Appraisal of Guidelines for Research and Evaluation version II instrument for the clinical guidelines and both A MeaSurement Tool to Assess Systematic Reviews and Risk of Bias in Systematic Reviews tools for the systematic reviews. A narrative synthesis approach will be used to assess the evidence of extracted data, primarily taking account of quality appraisal and recency of publication. Discussion: The synthesis of evidence will determine best practice for OCC early detection/screening by primary care dental healthcare professionals and will evaluate the relationship between clinical guidelines and the evidence base available from systematic reviews in this area

Assessment and prevention of behavioural and social risk factors associated with oral cancer: protocol for a systematic review of clinical guidelines and systematic reviews to inform primary care dental professionals

Background: Tobacco and alcohol are recognised as the major risk factors for both oral cavity (mouth) and oropharyngeal (throat) cancers, with increasing acceptance of the role of human papillomavirus (HPV) in the aetiology of oropharyngeal cancers. In addition, there is a significant increased risk for oral cancer among lower socioeconomic groups, males and older age groups. There is a growing evidence for the potential role of primary care professionals in smoking cessation and reducing alcohol-related harm. However, there are uncertainties about the best approaches/strategies to assess risk factors associated with oral cancer, effective components of preventive interventions for behaviour change and implementation strategies in primary care dental settings. Thus, in order to contribute to the prevention of oral cancer effectively, dental professionals need to assess patients on the major risk factors (tobacco, alcohol and HPV/sexual behaviours) and deliver appropriate prevention, taking into account the patient’s sociodemographic context. Aim: The study aims to synthesise evidence on the best practice for undertaking an assessment of major behavioural risk factors associated with oral cancer and delivering effective behaviour change preventive interventions (e.g. advice, counselling, patient recall, signposting/referral to preventive services) by dental professionals in primary care dental settings. Method: The study involves a systematic review and evidence appraisal. We will search for clinical guidelines and systematic reviews from the following databases: Cochrane Library, Ovid MEDLINE, EMBASE, Web of Science, PsychINFO, PubMed, TRIP and Google Scholar. We will also search websites of professional organisations/agencies and bibliographies/reference lists of selected papers. Quality will be assessed with the AGREE II (Appraisal of Guidelines for Research & Evaluation II) instrument for included clinical guidelines and the AMSTAR (A Measurement Tool to Assess Systematic Reviews) and ROBIS instruments for included systematic reviews. The best practice evidence will be assessed via a narrative synthesis of extracted data, considering publication quality. Discussion: This systematic review will synthesise evidence on the best practice for oral cancer risk factor assessment and prevention and evaluate the relationship between available clinical guidelines and the review evidence base. This collation of evidence will be useful for making recommendations for future intervention, research and guideline development

Maternal diet and gut microbiome composition modulate early-life immune development.

In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ-free mice with a consortium of 14 strains, fed them a standard fiber-rich chow or a fiber-free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber-rich diet, pups of fiber-deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin-foraging bacterium that can also use milk oligosaccharides. The pups of fiber-deprived dams exhibited an enrichment of colonic transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A. muciniphila from the community, but maintenance on the fiber-rich diet, was associated with reduced proportions of RORγt-positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development

Bio-inspired all-optical artificial neuromast for 2D flow sensing

We present the design, fabrication and testing of a novel all-optical 2D flow velocity sensor, inspired by a fish lateral line neuromast. This artificial neuromast consists of optical fibres inscribed with Bragg gratings supporting a fluid force recipient sphere. Its dynamic response is modelled based on the Stokes solution for unsteady flow around a sphere and found to agree with experimental results. Tuneable mechanical resonance is predicted, allowing a deconvolution scheme to accurately retrieve fluid flow speed and direction from sensor readings. The optical artificial neuromast achieves a low frequency threshold flow sensing of 5 mm s(-1) and 5 mu m s(-1) at resonance, with a typical linear dynamic range of 38 dB at 100 Hz sampling. Furthermore, the optical artificial neuromast is shown to determine flow direction within a few degrees

A randomised controlled trial investigating the effects of Mediterranean diet and aerobic exercise on cognition in cognitively healthy older people living independently within aged care facilities: The Lifestyle Intervention in Independent Living Aged Car

Background: The rapid ageing of the population is becoming an area of great concern, both globally and in Australia. On a societal level, the cost of supporting an ageing demographic, particularly with their associated medical requirements, is becoming an ever increasing burden that is only predicted to rise in the foreseeable future. The progressive decline in individuals\u27 cognitive ability as they age, particularly with respect to the ever increasing incidence of Alzheimer\u27s Disease (AD) and other cognitive complications, is in many respects one of the foundation stones of these concerns. There have been numerous observational studies reporting on the positive effects that aerobic exercise and the Mediterranean diet appear to have on improving cognitive ability. However, the ability of such interventions to improve cognitive ability, or even reduce the rate of cognitive ageing, has not been fully examined by substantial interventional studies within an ageing population. Methods: The LIILAC trial will investigate the potential for cognitive change in a cohort of cognitively healthy individuals, between the ages of 60 and 90 years, living in independent accommodation within Australian aged care facilities. This four-arm trial will investigate the cognitive changes which may occur as a result of the introduction of aerobic exercise and/or Mediterranean diet into individuals\u27 lifestyles, as well as the mechanisms by which these changes may be occurring. Participants will be tested at baseline and 6 months on a battery of computer based cognitive assessments, together with cardiovascular and blood biomarker assessments. The cardiovascular measures will assess changes in arterial stiffness and central pulse pressures, while the blood measures will examine changes in metabolic profiles, including brain derived neurotrophic factor (BDNF), inflammatory factors and insulin sensitivity. Conclusion: It is hypothesised that exercise and Mediterranean diet interventions, both individually and in combination, will result in improvements in cognitive performance compared with controls. Positive findings in this research will have potential implications for the management of aged care, particularly in respect to reducing the rate of cognitive decline and the associated impacts both on the individual and the broader community

Magnetic resonance imaging for assessment of cerebrovascular reactivity and its relationship to cognition: a systematic review

BACKGROUND: Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work. RESULTS: We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed. CONCLUSION: CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI

Innate lymphoid cell characterization in the rat and their correlation to gut commensal microbes.

Innate lymphoid cells (ILCs) are important for tissue immune homeostasis, and are thoroughly characterized in mice and humans. Here, we have performed in-depth characterization of rat ILCs. Rat ILCs were identified based on differential expression of transcription factors and lack of lineage markers. ILC3s represented the major ILC population of the small intestine, while ILC2s were infrequent but most prominent in liver and adipose tissue. Two major subsets of group 1 ILCs were defined. Lineage- T-bet+ Eomes+ cells were identified as conventional NK cells, while lineage- T-bet+ Eomes- cells were identified as the probable rat counterpart of ILC1s based on their selective expression of the ILC marker CD200R. Rat ILC1s were particularly abundant in liver and intestinal tissues, and were functionally similar to NK cells. Single-cell transcriptomics of spleen and liver cells confirmed the main division of NK cells and ILC1-like cells, and demonstrated Granzyme A as an additional ILC1 marker. We further report differential distributions of NK cells and ILCs along the small and large intestines, and the association of certain bacterial taxa to frequencies of ILCs. In conclusion, we provide a framework for future studies of ILCs in diverse rat experimental models, and novel data on the potential interplay between commensals and intestinal ILCs

Metabolic landscape of the male mouse gut identifies different niches determined by microbial activities.

Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolome along the gut of healthy colonized and germ-free male mice. With this map, we reveal a general shift from amino acids in the small intestine to organic acids, vitamins and nucleotides in the large intestine. We compare the metabolic landscapes in colonized versus germ-free mice to disentangle the origin of many metabolites in different niches, which in some cases allows us to infer the underlying processes or identify the producing species. Beyond the known impact of diet on the small intestinal metabolic niche, distinct spatial patterns suggest specific microbial influence on the metabolome in the small intestine. Thus, we present a map of intestinal metabolism and identify metabolite-microbe associations, which provide a basis to connect the spatial occurrence of bioactive compounds to host or microorganism metabolism