Woodwardfrederiksen7616

The intestinal epithelium limits host-luminal interactions and maintains gut homeostasis. Breakdown of the epithelial barrier and villous atrophy are hallmarks of coeliac disease. Besides the well characterized immune-mediated epithelial damage induced in coeliac mucosa, constitutional changes and early gluten direct effects disturb intestinal epithelial cells. The subsequent modifications in key epithelial signaling pathways leads to outnumbered immature epithelial cells that, in turn, facilitate epithelial dysfunction, promote crypt hyperplasia, and increase intestinal permeability. Consequently, underlying immune cells have a greater access to gluten, which boosts the proinflammatory immune response against gluten and positively feedback the epithelial damage loop. Gluten-free diet is an indispensable treatment for coeliac disease patients, but additional therapies are under development, including those that reinforce intestinal epithelial healing. In this chapter, we provide an overview of intestinal epithelial cell disturbances that develop during gluten intake in coeliac disease mucosa.Epithelial barriers are essential to maintain multicellular organisms well compartmentalized and protected from external environment. In the intestine, the epithelial layer orchestrates a dynamic balance between nutrient absorption and prevention of microorganisms, and antigen intrusion. Intestinal barrier function has been shown to be altered in coeliac disease but whether it contributes to the pathogenesis development or if it is merely a phenomenon secondary to the aberrant immune response is still unknown. The tight junction complexes are multiprotein cell-cell adhesions that seal the epithelial intercellular space and regulate the paracellular permeability of ions and solutes. These structures have a fundamental role in epithelial barrier integrity as well as in signaling mechanisms that control epithelial-cell polarization, the formation of apical domains and cellular processes such as cell proliferation, migration, differentiation, and survival. In coeliac disease, the molecular structures and function of tight junctions appear disrupted and are not completely recovered after treatment with gluten-free diet. Moreover, zonulin, the only known physiological regulator of the tight junction permeability, appears augmented in autoimmune conditions associated with TJ dysfunction, including coeliac disease. PF-3644022 solubility dmso This chapter will examine recent discoveries about the molecular architecture of tight junctions and their functions. We will discuss how different factors contribute to tight junction disruption and intestinal barrier impairment in coeliac disease. To conclude, new insights into zonulin-driven disruption of tight junction structures and barrier integrity in coeliac disease are presented together with the advancements in novel therapy to treat the barrier defect seen in pathogenesis.Celiac Disease (CeD) is an immune-mediated complex disease that is triggered by the ingestion of gluten and develops in genetically susceptible individuals. It has been known for a long time that the Human Leucocyte Antigen (HLA) molecules DQ2 and DQ8 are necessary, although not sufficient, for the disease development, and therefore other susceptibility genes and (epi)genetic events must participate in CeD pathogenesis. The advances in Genomics during the last 15 years have made CeD one of the immune-related disorders with the best-characterized genetic component. In the present work, we will first review the main Genome-Wide Association Studies (GWAS) carried out in the disorder, and emphasize post-GWAS discoveries, including diverse integrative strategies, SNP prioritization approaches, and insights into the Microbiome through the host Genomics. Second, we will explore CeD-related Epigenetics and Epigenomics, mostly focusing on the emerging knowledge of the celiac methylome, and the vast but yet under-explored non-coding RNA (ncRNA) landscape. We conclude that much has been done in the field although there are still completely unvisited areas in the post-Genomics of CeD. Chromatin conformation and accessibility, and Epitranscriptomics are promising domains that need to be unveiled to complete the big picture of the celiac Genome.

Exposure index (EI) is important to evaluate correct exposure in radiography and thus important for image quality. The purpose of this study was to evaluate whether the target exposure index (EI

) and deviation index (DI) were used efficiently.

Radiography departments in Iceland, using <10 years old equipment, were invited to participate. For each x-ray unit, admin users were asked about the use of EI

and data was gathered on EI

for five body parts (BP); lumbar spine, chest, hip, knee and hand. For each of the five BP, 100 examinations from the past year were selected randomly (or all, if<100). The EI from one predefined view was recorded and the corresponding DI calculated.

A total of ten x-ray units, from four manufacturers and located at eight departments, were included in the study. The departments involved are comprised of a university hospital, smaller hospitals, and miscellaneous private departments. Two departments (25%) had not set EI

, five (62.5%) used default values and only one had revised EI

values. In four departments (50%) radiographers favored "acceptable EI range" over DI. The mean EI was significantly different (p<0.05) from the EI

in the majority of the five BP, in four out of the six departments that had defined EI

. In total 30% of images from all departments combined had DI outside the range of-3.0<DI<+3.0. The standard deviation of DI was from 1.4 to 2.7.

The study shows that the EI

and DI are not used efficiently, regardless of equipment vendor or department characteristics.

Current recommendations on targeting the mean DI of 0 need to be reinforced. Theoretical knowledge and training need to be improved.

Current recommendations on targeting the mean DI of 0 need to be reinforced. Theoretical knowledge and training need to be improved.A possible association between iron and biofilm formation has been explored for a long time. Here, we focus on major recent advances that shed light on the mechanisms behind this relationship and discuss how siderophore-mediated iron acquisition may impact the virulence of important nosocomial pathogens.