Role of subclinical gut inflammation in the pathogenesis of spondyloarthritis

Subclinical gut inflammation occurring in patients affected by spondyloarthritis (SpA) is correlated with the severity of spine inflammation. Several evidences indicate that dysbiosis occurs in SpA, and that may modulate intestinal permeability and intestinal immune responses. The presence of intestinal dysbiosis is accompanied in SpA patients with the presence of zonulin-dependent alterations of gut-epithelial and gut-vascular barriers. The leakage of epithelial and endothelial surface layers is followed by the translocation of bacterial products, such as lipopolysaccharide and intestinal fatty acid binding protein, in the systemic circulation. These bacterial products may downregulate the expression of CD14 on circulating monocytes leading to an "anergic" phenotype. In the gut, IL-23 may induce the expansion of innate immune cells such as mucosal-associated invariant T cells, γδ T cells, and innate lymphoid cells of group 3 that through the interaction with MAdCAM1 may recirculate form the gut to the sites of SpA active inflammation. On the basis of these findings, gut inflammation observed in SpA patient seems to be not only an epiphenomenon of the on going systemic inflammatory process but may also represent the base camp in which inflammatory cells are activated and from whom they shuttle

A two-step approach for the analysis of hybrids in comparative social policy analysis: a nuanced typology of childcare policies

Typologies have represented an important tool for the development of comparative social policy research and continue to be widely used in spite of growing criticism of their ability to capture the complexity of welfare states and their internal heterogeneity. In particular, debates have focused on the presence of hybrid cases and the existence of distinct cross-national pattern of variation across areas of social policy. There is growing awareness around these issues, but empirical research often still relies on methodologies aimed at classifying countries in a limited number of unambiguous types. This article proposes a two-step approach based on fuzzy-set ideal type analysis for the systematic analysis of hybrids at the level of both policies (step 1) and policy configurations or combinations of policies (step 2). This approach is demonstrated by using the case of childcare policies in European economies. In the first step, parental leave policies are analysed using three methods-direct, indirect, and combinatory-to identify and describe specific hybrid forms at the level of policy analysis. In the second step, the analysis moves on to investigate the relationship between parental leave and childcare services. Clearly shows that many countries display characteristics normally associated with different types (hybrids and sub-types) . Therefore, this two-step approach demonstrates that disaggregated and aggregated analyses are equally important to account for hybrid welfare forms and make sense of the tensions and incongruences within and between policies

Qualitative Comparative Analysis as a Tool for Concept Clarification, Typology Building, and Contextualized Comparisons in Gender and Feminist Research

Qualitative Comparative Analysis (QCA) is a method for the systematic analysis of cases. A holistic view of cases and an approach to causality emphasizing complexity are some of its core features. Over the last decades, QCA has found application in many fields of the social sciences. In spite of this, its use in feminist research has been slower, and only recently QCA has been applied to topics related to social care, the political representation of women, and reproductive politics. Feminist researchers still privilege qualitative methods, in particular case studies, and are often sceptical of quantitative techniques (Spierings 2012). These studies show that the meaning and measurement of many gender concepts differ across countries and that the factors leading to feminist success and failure are context-specific. However, this scholarship struggles to systematically account for the ways in which these forces operate in different locations. The aim of this article is to demonstrate that QCA and related techniques contribute to enhance comparative analysis in ways which aligns with core ideas in gender and feminist studies. I begin by describing the main principles of QCA as a research strategy. The following sections draw on recent contributions in comparative social policy and politics literature to illustrate how it is used to deal with issues of concept clarification and measurement, policy complexity, the presence of hybrids and the development of normative types and context-sensitive causal analysis. Finally, this article concludes by discussing promising avenues for future applications of QCA in feminist research

Reconfigurable Antenna Systems: Platform implementation and low-power matters

Antennas are a necessary and often critical component of all wireless systems, of which they share the ever-increasing complexity and the challenges of present and emerging trends. 5G, massive low-orbit satellite architectures (e.g. OneWeb), industry 4.0, Internet of Things (IoT), satcom on-the-move, Advanced Driver Assistance Systems (ADAS) and Autonomous Vehicles, all call for highly flexible systems, and antenna reconfigurability is an enabling part of these advances. The terminal segment is particularly crucial in this sense, encompassing both very compact antennas or low-profile antennas, all with various adaptability/reconfigurability requirements. This thesis work has dealt with hardware implementation issues of Radio Frequency (RF) antenna reconfigurability, and in particular with low-power General Purpose Platforms (GPP); the work has encompassed Software Defined Radio (SDR) implementation, as well as embedded low-power platforms (in particular on STM32 Nucleo family of micro-controller). The hardware-software platform work has been complemented with design and fabrication of reconfigurable antennas in standard technology, and the resulting systems tested. The selected antenna technology was antenna array with continuously steerable beam, controlled by voltage-driven phase shifting circuits. Applications included notably Wireless Sensor Network (WSN) deployed in the Italian scientific mission in Antarctica, in a traffic-monitoring case study (EU H2020 project), and into an innovative Global Navigation Satellite Systems (GNSS) antenna concept (patent application submitted). The SDR implementation focused on a low-cost and low-power Software-defined radio open-source platform with IEEE 802.11 a/g/p wireless communication capability. In a second embodiment, the flexibility of the SDR paradigm has been traded off to avoid the power consumption associated to the relevant operating system. Application field of reconfigurable antenna is, however, not limited to a better management of the energy consumption. The analysis has also been extended to satellites positioning application. A novel beamforming method has presented demonstrating improvements in the quality of signals received from satellites. Regarding those who deal with positioning algorithms, this advancement help improving precision on the estimated position

Pathogenesis of polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance between Th17 and Treg cells. Disturbed B cell distribution and function have been also demonstrated in PMR patients suggesting a pathogenesis more complex than previously imagined. In this review we will discuss the recent findings regarding the pathogenesis of PMR

Histopathology of the gut in rheumatic diseases

The gastrointestinal tract regulates the trafficking of macromolecules between the environment and the host through an epithelial barrier mechanism and is an important part of the immune system controlling the equilibrium between tolerance and immunity to non-self-antigens. Various evidence indicates that intestinal inflammation occurs in patients with rheumatic diseases. In many rheumatic diseases intestinal inflammation appears to be linked to dysbiosis and possibly represents the common denominator in the pathogenesis of different rheumatic diseases. The continuative interaction between dysbiosis and the intestinal immune system may lead to the aberrant activation of immune cells that can re-circulate from the gut to the sites of extraintestinal inflammation as observed in patients with ankylosing spondylitis. The exact contribution of genetic factors in the development of intestinal inflammation in rheumatic diseases needs to be clarified

Identification and characterization of MUS81 point mutations that abolish interaction with the SLX4 scaffold protein

AbstractMUS81-EME1 is a conserved structure-selective endonuclease with a preference for branched DNA substrates in vitro that correspond to intermediates of DNA repair. Cells lacking MUS81 or EME1 show defects in the repair of DNA interstrand crosslinks (ICL) resulting in hypersensitivity to agents such as mitomycin C. In metazoans, a proportion of cellular MUS81-EME1 binds the SLX4 scaffold protein, which is itself instrumental for ICL repair. It was previously reported that mutations in SLX4 that abolished interaction with MUS81 affected ICL repair in human cells but not in murine cells. In this study we looked the other way around by pinpointing amino acid residues in MUS81 that when mutated abolish the interaction with SLX4. These mutations fully rescued the mitomycin C hypersensitivity of MUS81 knockout murine cells, but they were unable to rescue the sensitivity of two different human cell lines defective in MUS81. These data support an SLX4-dependent role for MUS81 in the repair, but not the induction of ICL-induced double-strand breaks. This study sheds light on the extent to which MUS81 function in ICL repair requires interaction with SLX4

Autophagy in the pathogenesis of ankylosing spondylitis

The pathogenesis of ankylosing spondylitis (AS) is not well understood, and treatment options have met with limited success. Autophagy is a highly conserved mechanism of controlled digestion of damaged organelles within a cell. It helps in the maintenance of cellular homeostasis. The process of autophagy requires the formation of an isolation membrane. They form double-membraned vesicles called “autophagosomes” that engulf a portion of the cytoplasm. Beyond the role in maintenance of cellular homeostasis, autophagy has been demonstrated as one of the most remarkable tools employed by the host cellular defense against bacteria invasion. Autophagy also affects the immune system and thus is implicated in several rheumatic disease processes. In this article, we explore the potential role of autophagy in the pathogenesis of AS

Invariant NKT cells and rheumatic disease: Focus on primary sjogren syndrome

Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity