[A painful periapical radiopacity in the lower jaw]. / Een pijnlijke periapicale radiopaciteit in de onderkaak.

A periapical radiopacity is frequently encountered by chance on a conventional periapical or panoramic x-ray. However, local pain and/or swelling in the area of a radiopacity is seldom seen. Here, we report on 2 cases of patients referred to the oral and maxillofacial surgeon with a painful periapical radiopacity in the lower jaw. The clinically and radiologically assumed diagnosis was a cementoblastoma, which was confirmed by histopathological examination following its surgical removal. A cementoblastoma is a rare, benign odontogenic tumor, mostly found in patients younger than 30. Treatment consists of surgical removal of the tumor, almost always together with the attached tooth. The recurrence rate after complete removal is approximately 12%. A cementoblastoma is clinically distinguished from other periapical radiopacities by local pain and sometimes swelling and radiologically by a relationship with the roots of a (pre)molar, a radiolucent rim surrounding the opacity, bone and/or root resorption and expansive growth.

Cortrak® duodenal tube placements: A solution for more patients? A preliminary survey to the introduction of electromagnetic-guided placement of naso-duodenal feeding tubes.

RATIONALE: The Cortrak® feeding tube, an electromagnetic (EM) guided feeding tube which is placed by a trained nurse at the patient's bedside, is reported to be a safe, patient friendly and cost effective answer to the disadvantages of endoscopic placement of naso-duodenal feeding tubes. However, this procedure requires a learning curve and regular practice. This study aims to evaluate whether introducing Cortrak® feeding tube placement would be profitable in a tertiary referral academic hospital. METHODS: We re-evaluated all endoscopically placed post-pyloric feeding tubes in the years 2012-2013. Taking into consideration training for nurses to learn how to place Cortrak® feeding tubes, strict inclusion criteria were formulated for the initial retrospective analysis: age 18 years or older, normal GI anatomy and non-ICU admitted patients. As a secondary analysis we also evaluated ICU patients (age >18 and normal upper GI tract). RESULTS: Patient records of 487 duodenal feeding tube placements in 331 patients were evaluated; 125 non-ICU placements (in 90 patients) and 84 ICU placements (in 75 ICU patients) fulfilled the inclusion criteria. Main reasons for exclusion were: abnormalities of the upper GI tract (n = 176) and endoscopy for diagnostic reasons (n = 74). Main indications for placements were gastroparesis (37%) or insufficient food intake (20%). For secondary analysis, 84 placements in 75 ICU patients were re-evaluated, with main indication gastroparesis (62%). CONCLUSION: In our hospital, at least one quarter of the duodenal tube placements would qualify for Cortrak® placement in the initial phase. Once routine has been built up and also ICU patients could be considered, half or more patients requiring a naso-duodenal feeding tube would qualify for Cortrak® placement, adding up to 3 placements per week. The findings of this study may help to decide on the profitability of introducing this method in our own hospital. The next step will be to perform a cost-benefit analysis to study whether implementing Cortrak® in practice is cost-effective and feasible.

The microbiome-systemic diseases connection.

The human microbiome consists of all microorganisms occupying the skin, mucous membranes and intestinal tract of the human body. The contact of the mucosal immune system with the human microbiome is a balanced interplay between defence mechanisms of the immune system and symbiotic or pathogenic microbial factors, such as microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, the immune system is deranged to a chronic inflammatory state and autoantibodies are an important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome can lead to local mucosal inflammation and increased intestinal permeability. Proinflammatory lymphocytes and cytokines can spread to the systemic circulation and increase the risk of inflammation at distant anatomical sites, such as the joints or salivary glands. Increased intestinal permeability increases antigen exposure and the risk of autoantibody production. If the human microbiome indeed plays such a critical role in SADs, this finding holds a great promise for new therapeutic strategies, such as diet interventions and probiotics and prebiotics. This review provides a background on the human microbiome and mucosal immunity in the gut and oral cavity and gives a summary of the current knowledge on the microbiome-SADs connection.

Glucocorticoids differentially regulate the expression of CRFR1 and CRFR2α in MIN6 insulinoma cells and rodent islets.

Urocortin 3 (Ucn 3), member of the corticotropin-releasing factor (CRF) family of peptide hormones, is released from ß-cells to potentiate insulin secretion. Ucn 3 activates the CRF type-2 receptor (CRFR2) but does not activate the type-1 receptor (CRFR1), which was recently demonstrated on ß-cells. While the direct actions of Ucn 3 on insulin secretion suggest the presence of cognate receptors within the islet microenvironment, this has not been established. Here we demonstrate that CRFR2α is expressed by MIN6 insulinoma cells and by primary mouse and human islets, with no detectable expression of CRFR2ß. Furthermore, stimulation of MIN6 cells or primary mouse islets in vitro or in vivo with glucocorticoids (GCs) robustly and dose-dependently increases the expression of CRFR2α, while simultaneously inhibiting the expression of CRFR1 and incretin receptors. Luciferase reporters driven by the mouse CRFR1 or CRFR2α promoter in MIN6 cells confirm these differential effects of GCs. In contrast, GCs inhibit CRFR2α promoter activity in HEK293 cells and inhibit the expression of CRFR2ß in A7r5 rat aortic smooth muscle cells and differentiated C2C12 myotubes. These findings suggest that the GC-mediated increase of CRFR2α depends on the cellular context of the islet and deviates from the GC-mediated suppression of CRFR1 and incretin receptors. Furthermore, GC-induced increases in CRFR2α expression coincide with increased Ucn 3-dependent activation of cAMP and MAPK pathways. We postulate that differential effect of GCs on the expression of CRFR1 and CRFR2α in the endocrine pancreas represent a mechanism to shift sensitivity from CRFR1 to CRFR2 ligands.

Endurance exercise differentially stimulates heart and axial muscle development in zebrafish (Danio rerio).

Mechanical load is an important factor in the differentiation of cells and tissues. To investigate the effects of increased mechanical load on development of muscle and bone, zebrafish were subjected to endurance swim training for 6 h/day for 10 wk starting at 14 days after fertilization. During the first 3 wk of training, trained fish showed transiently increased growth compared with untrained (control) fish. Increased expression of proliferating cell nuclear antigen suggests that this growth is realized in part through increased cell proliferation. Red and white axial muscle fiber diameter was not affected. Total cross-sectional area of red fibers, however, was increased. An improvement in aerobic muscle performance was supported by an increase in myoglobin expression. At the end of 10 wk of training, heart and axial muscle showed increased expression of the muscle growth factor myogenin and proliferating cell nuclear antigen, but there were major differences between cardiac and axial muscle. In axial muscle, expression of the "slow" types of myosin and troponin C was increased, together with expression of erythropoietin and myoglobin, which enhance oxygen transport, indicating a shift toward a slow aerobic phenotype. In contrast, the heart muscle shifts to a faster phenotype but does not become more aerobic. This suggests that endurance training differentially affects heart and axial muscle.

Effects of decreased muscle activity on developing axial musculature in nicb107 mutant zebrafish (Danio rerio).

The present paper discusses the effects of decreased muscle activity (DMA) on embryonic development in the zebrafish. Wild-type zebrafish embryos become mobile around 18 h post-fertilisation, long before the axial musculature is fully differentiated. As a model for DMA, the nic(b107) mutant was used. In nic(b107) mutant embryos, muscle fibres are mechanically intact and able to contract, but neuronal signalling is defective and the fibres are not activated, rendering the embryos immobile. Despite the immobility, distinguished slow and fast muscle fibres developed at the correct location in the axial muscles, helical muscle fibre arrangements were detected and sarcomere architecture was generated. However, in nic(b107) mutant embryos the notochord is flatter and the cross-sectional body shape more rounded, also affecting muscle fibre orientation. The stacking of sarcomeres and myofibril arrangement show a less regular pattern. Finally, expression levels of several genes were changed. Together, these changes in expression indicate that muscle growth is not impeded and energy metabolism is not changed by the decrease in muscle activity but that the composition of muscle is altered. In addition, skin stiffness is affected. In conclusion, the lack of muscle fibre activity did not prevent the basal muscle components developing but influenced further organisation and differentiation of these components.

Identification and characterisation of two runx2 homologues in zebrafish with different expression patterns.

Genome and gene duplications are considered to be the impetus to generate new genes, as the presence of multiple copies of a gene allows for paralogues to adopt novel function. After at least two rounds of genome/gene duplication, the Runt gene family consists of three members in vertebrates, instead of one in invertebrates. One of the family members, Runx2, plays a key role in the development of bone, a tissue that first occurs in vertebrates. The family has thus gained new gene function in the course of evolution. Two Runx2 genes were cloned in the vertebrate model system the zebrafish (Danio rerio). The expression patterns of the two genes differ and their kinetics differ up to four fold. In addition, splice forms exist that are novel when compared with mammals. Together, these findings comprise opportunities for selection and retention of the paralogues towards divergent and possibly new function.