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Byline: B. Kuttler (1), K. Rosing (1), M. Lehmann (2), J. Brock (2), H. J. Hahn (1) Keywords: Key words BB rat; Islet transplantation; Rejection; Disease recurrence; Immunotherapy Abstract: Grafting autoimmune-diabetic recipients with allogeneic islets, graft rejection and disease recurrence as major problems of reaching indefinite survival and tolerance induction have to be solved. Anti-CD25 and anti-CD4 monoclonal antibodies were successfully used after allogeneic islet transplantation in experimentally diabetic rats. A temporary anti-CD25 therapy also prevented disease recurrence in autoimmune-diabetic BB rats, while this was not yet reported for an anti-CD4 treatment. In autoimmune-diabetic NOD mice disease recurrence can be successfully treated using an anti-CD4 monoclonal antibody. We, therefore, compared the efficacy of a short-term anti-CD25 and anti-CD4 treatment regarding the prevention of allograft rejection and disease recurrence in autoimmune-diabetic BB/OK rats. Both monoclonal antibodies were combined with low doses of Cyclosporin A. Untreated BB/OK rats relapsed into hyperglycaemia within 3 weeks independent of the islet donor, LEW.1A, LEW.1BB/OK or BB/OK rats. However, after grafting MHC-identical allogeneic (LEW.1BB/OK) or syngeneic (BB/OK) islets we observed about 30% spontaneous acceptance. Both the anti-CD25 and anti-CD4 therapy significantly prolonged the survival of allogeneic grafted islets. After MHC-identical allogeneic and syngeneic islet transplantation the temporary immunotherapy increased the proportion of permanent acceptors to 63% and 75%, respectively. The efficacy of both treatment strategies in prolonging allograft survival and prevention of disease recurrence was identical. In summary, anti-CD25 as well as anti-CD4 therapy prevented autoimmune but not allogeneic islet destruction in autoimmune-diabetic BB/OK rats. In conclusion, targeting different immune cells by monoclonal antibodies with different specificities can lead to very similar results with respect to an interruption of allograft rejection and autoimmune reaction. Author Affiliation: (1) Institute of Pathophysiology, (formerly Institute of Diabetes 'G. Karsch') Ernst-Moritz-Arndt-University of Greifswald, Greifswalder Strasse 11a, D-17495 Karlsburg, Germany, DE (2) Institute of Medical Biochemistry, University of Rostock, Germany, DE

Objective: To explore barriers and facilitators to oral disease prevention in Danish dental care from a multi-stakeholder perspective. Methods: Eleven semi-structured focus groups and interviews about Danish oral healthcare were conducted with 27 stakeholders (general public, dental teams, dental policy makers) in Copenhagen. Transcripts were analyzed using deductive thematic analysis independently by KR and HL, supervised by JC and KVC. Results: Seven broad themes were identified, including both barriers and facilitators: Knowledge and attitudes, Education and training, Regulation, Incentivization, Multidisciplinary approach, Access to care and the Dental professional-patient relationship. Whilst all themes were relevant to each group of stakeholders, the salient driver within each theme was different for each group. Conclusions: Stakeholder perspectives on the Danish Oral health care system suggest the following are important features for a preventively focused system: (a) Involving all stakeholders in oral healthcare planning. (b) Securing sufficient and ongoing briefing regarding disease prevention for all stakeholders. (c) Regulatory support and creation of incentives to promote and facilitate implementation of disease prevention. (d) Appropriate prevention for disadvantaged groups within society which may be possible to a higher degree by means of multidisciplinary collaboration. (e) Personal relations between the patient and the professional based on mutual trust. [ABSTRACT FROM AUTHOR]

Background Lichen planus ( LP) is a chronic inflammatory disease of unknown aetiology affecting the skin and oral mucosa. Oral lichenoid lesions ( OLLs), like oral contact reactions, may resemble oral lichen planus ( OLP) both clinically and histopathologically. As OLP and OLL are hyperkeratotic diseases and filaggrin is essential to keratinization, the distribution of filaggrin may be altered in these lesions. Objectives To investigate whether patients with OLP/ OLL have (i) altered distribution of filaggrin in the oral mucosa; (ii) a higher incidence of mutations in the filaggrin gene ( FLG); (iii) active dermatoses, apart from cutaneous LP, than healthy controls; and (iv) patients with OLP/ OLL and a defect in the FLG have more widespread oral lesions and report more symptoms than OLP/ OLL patients without a concomitant defect in the FLG. Methods Forty-nine Caucasian patients (42 women and 7 men, mean age 61.0 ± 10.3 years), with symptomatic OLP, OLL or stomatitis, and 29 matched healthy controls underwent a clinical oral and dermatological examination, oral mucosal biopsy and filaggrin genotyping (testing for R2447X, R501X, 2282del4). Smear tests for Candida spp. were performed in all patients to exclude oral candidiasis. Immunohistochemistry were performed using poly- and monoclonal filaggrin antibodies. Results The immunoreactivity for filaggrin was significantly more intense in the oral mucosa in the patients with OLP/ OLL compared with healthy controls ( P = 0.000025). No difference was noted in the incidence of defects in the FLG and active dermatoses between patients and healthy controls. No difference was noted in extension and number of symptoms reported by patients with OLP/ OLL with or without a concomitant defect in the FLG. Conclusion OLP/ OLL is associated with an altered distribution of filaggrin in the oral mucosa independently of defects in the FLG. Patients with OLP/ OLL did not display more active dermatoses other than cutaneous LP when compared to healthy controls. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to compare the microbiota of stimulated whole saliva samples from patients with severe hyposalivation to samples from individuals with normal whole saliva flow rates. It was hypothesized that the two groups differ with regard to salivary bacterial profiles. Methods This cross-sectional study included 36 participants (24 females and 12 males, mean age 58.5 years) with severe hyposalivation and 36 gender-, age-, and geographically matched participants with normal salivary secretion from the Danish Health Examination Survey ( DANHES). The microbiota of stimulated whole saliva samples was characterized by HOMI NGS. Results The two groups had comparable caries experience measured by decayed, missed, filled surfaces/teeth and decayed, missed, filled root surfaces as well as active caries lesions. In addition, no single probe target was present with a significant difference in frequency or proportional presence between groups. Furthermore, data reduction by principal component analysis and correspondence analysis showed comparable bacterial community profiles between groups. Conclusions The results indicate that the salivary bacterial profiles of patients with severe hyposalivation do not differ from those of individuals with normal salivary secretion, when there are virtually no untreated active caries lesions present in the oral cavity. [ABSTRACT FROM AUTHOR]