How do spatially distinct frequency specific MEG networks emerge from one underlying structural connectome? The role of the structural eigenmodes

Functional networks obtained from magnetoencephalography (MEG) from different frequency bands show distinct spatial patterns. It remains to be elucidated how distinct spatial patterns in MEG networks emerge given a single underlying structural network. Recent work has suggested that the eigenmodes of the structural network might serve as a basis set for functional network patterns in the case of functional MRI. Here, we take this notion further in the context of frequency band specific MEG networks. We show that a selected set of eigenmodes of the structural network can predict different frequency band specific networks in the resting state, ranging from delta (1–4 Hz) to the high gamma band (40–70 Hz). These predictions outperform predictions based from surrogate data, suggesting a genuine relationship between eigenmodes of the structural network and frequency specific MEG networks. We then show that the relevant set of eigenmodes can be excited in a network of neural mass models using linear stability analysis only by including delays. Excitation of an eigenmode in this context refers to a dynamic instability of a network steady state to a spatial pattern with a corresponding coherent temporal oscillation. Simulations verify the results from linear stability analysis and suggest that theta, alpha and beta band networks emerge very near to the bifurcation. The delta and gamma bands in the resting state emerges further away from the bifurcation. These results show for the first time how delayed interactions can excite the relevant set of eigenmodes that give rise to frequency specific functional connectivity patterns

Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria

BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens

Classroom support for inclusion in England and Ireland: an evaluation of contrasting models

When reporting on those conditions which they perceive as necessary for the inclusion of students with special educational needs, teachers often refer to the importance of additional adult support in the classroom. The deployment of teaching assistants in England and special needs assistants in Ireland has been regarded as an important factor in supporting national policies for inclusion in both countries. This article reports on research which through survey and interview methods investigated the working practices of these colleagues and discusses the different approaches to their deployment in schools. It is suggested that whilst there are clear distinctions between the operations of the teaching assistant in England and the special needs assistant in Ireland, both play a distinct and essential role in the development of inclusive schooling. The article considers how two distinctive models of classroom support have emerged and the different ways in which they impact upon inclusion. Consideration is given to the changes which are taking place in the development of classroom teams and the ways in which this may impact upon current and future inclusion agenda

Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera >= 25-30 nmol/L: a dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude

Background: In the absence of dose-response data, Dietary Reference Values for vitamin D in nonpregnant adults are extended to pregnancy. Objective: The aim was to estimate vitamin D intake needed to maintain maternal 25-hydroxyvitamin D [25(OH)D] in late gestation at a concentration sufficient to prevent newborn 25(OH)D = 25-30 nmol/L. Results: Mean +/- SD baseline 25(OH)D was 54.9 +/- 10.7 nmol/L. Total vitamin D intakes at the study endpoint (36 wk of gestation) were 12.1 +/- 8.0, 21.9 +/- 5.3, and 33.7 +/- 5.1 mu g/d in the placebo and 10-mu g and 20-mu g vitamin D-3 groups, respectively; and 25(OH)D was 24.3 +/- 5.8 and 29.2 +/- 5.6 nmol/L higher in the 10- and 20-mu g groups, respectively, compared with placebo (P = 50 nmol/L, 95% of cord sera were >= 30 nmol/L and 99% were > 25 nmol/L. The estimated vitamin D intake required to maintain serum 25(OH)D at >= 50 nmol/L in 97.5% of women was 28.9 mu g/d. Conclusions: Thirty micrograms of vitamin D per day safely maintained serum 25(OH)D concentrations at >= 50 nmol/L in almost all white-skinned women during pregnancy at a northern latitude, which kept 25(OH)D at > 25 nmol/L in 99% and >= 30 nmol/L in 95% of umbilical cord sera

Case report: hypergranular platelets in vaccine-induced thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination

Background: Vaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery.Case presentation: A 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis (CVST). Peripheral blood smears revealed the presence of large, hypergranular platelets. Following treatment, hematological parameters returned to normal ranges over the study period. Anti-PF4 antibodies remained persistently high up to 90 days post-admission. Two days after admission, VITT platelets contained more granules per-platelet when compared to day 72 and healthy platelets. Additionally, maximal ATP release (marker of dense-granule release) was increased on day 2 compared to day 72 and healthy control platelets.Conclusion: This study highlights a previously unreported observation of platelet hypergranularity in VITT which may contribute to the thrombotic risk associated with VITT. Optimal approaches to monitoring recovery from VITT over time remains to be determined but our findings may help inform therapeutic decisions relating to anticoagulation treatment in this novel pathology.</div