Editorial: The Interplay Between Immune Activation and Cardiovascular Disease During Infection, Autoimmunity and Aging: The Role of T Cells

Chronic activation of cells of the immune system including T cells and systemic inflammation are well known risk factors for cardiovascular disease (CVD). Many human pathological conditions including viral infections, autoimmune diseases and aging are recognized drivers of increased risk of CVD. Among viral infections, Cytomegalovirus (CMV) infection is a contributing risk element to the existing traditional risk factors of atherogenesis; Influenza infection is correlated with ncreased the risk of cardiovascular events leading to deaths and HIV infection is an independent predictor of cardiovascular risk. The pandemic of SARS-COV2 infection showed that the severe presentation of the disease manifests with vascular damage and cardiovascular events. Autoimmune and chronic inflammatory diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic disease are also associated with cardiovascular disease. Lastly, in adults over 65 years, the accumulation of age-related phenotypic and functional alterations in immune cells parallels with a decline of the cardiovascular system with an increased incidence of cardiovascular disease. The mechanisms behind are not well defined, and while the role of innate immune cells has been established, the involvement of T cells in promoting vascular pathology and cardiovascular disease has emerged more recently (1). Chronic systemic inflammation and increased circulating levels of cytokines and chemokines can indeed contribute to vascular damage by promoting endothelial cell activation and oxidative stress thus linking to the increased risk of CVD (2, 3). Activation of endothelial cells promotes recruitment of circulating immune cells including T cells that will be activated and differentiate into distinct effector cells contributing to the pathology of the disease (4–6). Endothelial cells in this context have also been proposed to act as “semiprofessional” antigen presenting cells (APC) presenting antigens and providing several costimulatory signals to T cells leading to T cell activation especially at sites defined as endothelium-dependent microvascular reactivity sites by Laser Doppler Flowmetry Assessment (7). A milestone in the understanding the role of T cells in promoting vascular inflammation has been reached with the characterization of the immune cell infiltrate in human atherosclerotic plaque by scRNA-seq technology which defined the main subsets of T cells in atherosclerosis (8). This data paved the way for further investigations about the role of T cells as a putative mechanistic link in pathologies associated with an increased risk of CVD. The proposed mechanisms by which T cells contribute to the pathology of the disease include dysregulated T helper and CD8 T cell function, expansion of terminally differentiated cytotoxic effectors CD4+ CD28- T cells and impaired Tregs function. This Research Topic has the aim to provide an overview of the latest advances in the study of the role of T cell activation and endothelial inflammation in cardiovascular risk and disease in the context of infection, autoimmunity and aging. The Research Topic highlights the emerging common and distinctive features of the putative immune mechanistic links between the pathophysiological conditions and the associated cardiovascular disease. The Research Topic comprises 11 articles, original research articles, 5 review and one systematic review and was divided into 3 sections. 1. Endothelial inflammation and T cell activation in CVD associated with infection. 2. T cell mechanisms involved in CVD associated with autoimmune diseases. 3. The immunology of cardiovascular disease during aging

T cell subpopulations in the physiopathology of fibromyalgia : Evidence and perspectives

Fibromyalgia is one of the most important \u201crheumatic\u201d disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1\u3b2, IL-6, and TNF\u251. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia

Effects of parameterization and knot placement techniques on primal and mixed isogeometric collocation formulations of spatial shear-deformable beams with varying curvature and torsion

We present a displacement-based and a mixed isogeometric collocation (IGA-C) formulation for free-form, three-dimensional, shear-deformable beams with high and rapidly-varying curvature and torsion. When such complex shapes are concerned, the approach used to build the IGA geometric model becomes relevant. Although IGA-C has been so far successfully applied to a wide range of problems, the effects that different parameterization and knot placement techniques may have on the accuracy of collocation-based formulations is still an unexplored field. To fill this gap, primal and mixed formulations are used combining two parameterization methods (chord-length and equally spaced) with two knot placement techniques (uniformly spaced and De Boor). With respect to the space-varying Frenet local frame, we derive the strong form of the governing equations in a compact form through the definition of two matrix operators conveniently used to perform first and second order derivatives of the vector fields involved in the formulations. This approach is very efficient and easy to implement within a collocation-based scheme. Several challenging numerical experiments allow to test the different considered parameterizations and knot placement techniques, revealing in particular that with the primal formulation an equally spaced parameterization is definitively the most recommended choice and it should always be used with an approximation degree of, at least, , although some caution must be adopted when very high Jacobians and small curvatures occur. The same holds for the mixed formulation, with the difference that is enough to yield accurate results

If it does take a village to raise a child, how should the village do it? Insights from the kids in places initiative

Cross-sector collaborations are some of the strategies used to promote early childhood development and wellbeing. Without these collaborations, key services for families with young children may be missed or even duplicated. By drawing from experiences in Canada and Italy, we share findings from a study that aimed to understand the factors that make cross-sector collaborations (CSC) succeed or fail. Specifically, the study focused on understanding how CSC promoting early child development are created, maintained, and consolidated; and on identifying the social psychological, organizational, and economic aspects of CSC that help or hinder their functioning. Based on qualitative analysis of data gathered from four focus groups and thirteen interviews conducted across seven Canadian and Italian communities, we conclude that the success of CSC depend of a series of factors that transcend context, language and culture

Error-estimate-based adaptive integration for immersed isogeometric analysis

The Finite Cell Method (FCM) together with Isogeometric analysis (IGA) has been applied successfully in various problems in solid mechanics, in image-based analysis, fluid–structure interaction and in many other applications. A challenging aspect of the isogeometric finite cell method is the integration of cut cells. In particular in three-dimensional simulations the computational effort associated with integration can be the critical component of a simulation. A myriad of integration strategies has been proposed over the past years to ameliorate the difficulties associated with integration, but a general optimal integration framework that suits a broad class of engineering problems is not yet available. In this contribution we provide a thorough investigation of the accuracy and computational effort of the octree integration scheme. We quantify the contribution of the integration error using the theoretical basis provided by Strang's first lemma. Based on this study we propose an error-estimate-based adaptive integration procedure for immersed isogeometric analysis. Additionally, we present a detailed numerical investigation of the proposed optimal integration algorithm and its application to immersed isogeometric analysis using two- and three-dimensional linear elasticity problems

Skeleton-stabilized ImmersoGeometric Analysis for incompressible viscous flow problems

A Skeleton-stabilized ImmersoGeometric Analysis technique is proposed for incompressible viscous flow problems with moderate Reynolds number. The proposed formulation fits within the framework of the finite cell method, where essential boundary conditions are imposed weakly using a Nitsche-type method. The key idea of the proposed formulation is to stabilize the jumps of high-order derivatives of variables over the skeleton of the background mesh. The formulation allows the use of identical finite-dimensional spaces for the approximation of the pressure and velocity fields in immersed domains. The stability issues observed for inf-sup stable discretizations of immersed incompressible flow problems are avoided with this formulation. For B-spline basis functions of degree $k$ with highest regularity, only the derivative of order $k$ has to be controlled, which requires specification of only a single stabilization parameter for the pressure field. The Stokes and Navier-Stokes equations are studied numerically in two and three dimensions using various immersed test cases. Oscillation-free solutions and high-order optimal convergence rates can be obtained. The formulation is shown to be stable even in limit cases where almost every elements of the physical domain is cut, and hence it does not require the existence of interior cells. In terms of the sparsity pattern, the algebraic system has a considerably smaller stencil than counterpart approaches based on Lagrange basis functions. This important property makes the proposed skeleton-stabilized technique computationally practical. To demonstrate the stability and robustness of the method, we perform a simulation of fluid flow through a porous medium, of which the geometry is directly extracted from 3D $\mu{CT}$ scan data

Performance evaluation of a multicast-based solution for wireless resources discovery N. Blefari-Melazzi

Abstract --An improved IP network service (e.g., for real time services) is expected in the near future in both wired and wireless environment. In this regard, the handover capabilities are extremely important and challenging, in particular if their use in operation must be seamless. One of the main steps to achieve seamless handover is the quick discovery of IP addresses and service capabilities of candidate access routers to hand over to. In this paper, we present a push-mode-multicast based solution to discover and timely update information about wireless resources. We evaluate the effectiveness of the proposed approach in terms of signaling burden and discovery time with respect to solutions already presented in literature

Residual-based error estimation and adaptivity for stabilized immersed isogeometric analysis using truncated hierarchical B-splines

We propose an adaptive mesh refinement strategy for immersed isogeometric analysis, with application to steady heat conduction and viscous flow problems. The proposed strategy is based on residual-based error estimation, which has been tailored to the immersed setting by the incorporation of appropriately scaled stabilization and boundary terms. Element-wise error indicators are elaborated for the Laplace and Stokes problems, and a THB-spline-based local mesh refinement strategy is proposed. The error estimation .and adaptivity procedure is applied to a series of benchmark problems, demonstrating the suitability of the technique for a range of smooth and non-smooth problems. The adaptivity strategy is also integrated in a scan-based analysis workflow, capable of generating reliable, error-controlled, results from scan data, without the need for extensive user interactions or interventions.Comment: Submitted to Journal of Mechanic

Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis