Background and ObjectivePeri‐implantitis is a destructive inflammatory process characterized by destruction of the implant‐supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri‐implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples.Material and methodsHuman macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell‐culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin‐1β (IL‐1β) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively.ResultsTi ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL‐1β release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 μm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 μm) to stimulate secretion of IL‐1β from human macrophages in vitro.ConclusionTi ions form particles that act as secondary stimuli for a proinflammatory reaction.

The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

Summary Insulin resistance is a hallmark of diabetes and an unmet clinical need. Insulin inhibits hepatic glucose production and promotes lipogenesis by suppressing FOXO1-dependent activation of G6pase and inhibition of Glucokinase, respectively. The tight coupling of these events poses a dual conundrum: mechanistically, as the FOXO1 corepressor of Glucokinase is unknown; and clinically, as inhibition of glucose production is predicted to increase lipogenesis. Here we report that SIN3A is the insulin-sensitive FOXO1 corepressor of Glucokinase. Genetic ablation of SIN3A abolishes nutrient regulation of Glucokinase, without affecting other FOXO1 target genes, and lowers glycemia without concurrent steatosis. To extend this work, we executed a small molecule screen and discovered selective inhibitors of FOXO-dependent glucose production devoid of lipogenic activity in hepatocytes. In addition to identifying a novel mode of insulin action, these data raise the possibility of developing selective modulators of unliganded transcription factors to dial out adverse effects of insulin sensitizers.

The JP2 genotype of A. actinomycetemcomitans is strongly associated with the progression of AL.

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A. actinomycetemcomitans and AL were frequently found in Ghanaian adolescents. The school type was the strongest predictor of both presence of A. actinomycetemcomitans and AL.

Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

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