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Periodontitis is an inflammatory disease caused by pathogenic microorganisms, such as Porphyromonas gingivalis, and characterized by the destruction of the periodontium. Obese individuals have an increased risk for periodontitis and show decreased serum levels of adiponectin. This in-vitro study was established to examine whether adiponectin modulates critical effects of lipopolysaccharide (LPS) from P. gingivalis on oral epithelial cells (OECs). The presence of adiponectin and its receptors in human gingival tissue samples and OECs was analyzed by immunohistochemistry and PCR. Furthermore, OECs were treated with LPS and/or adiponectin for up to 72 h, and the gene expression and protein synthesis of pro- and anti-inflammatory mediators, matrix metalloproteinases (MMPs) and growth factors were analyzed by real-time PCR and ELISA. Additionally, cell proliferation, differentiation and in-vitro wound healing were studied. The nuclear translocation of NFκB was investigated by immunofluorescence. Gingival tissue sections showed a strong synthesis of adiponectin and its receptors in the epithelial layer. In cell cultures, LPS induced a significant up-regulation of interleukin (IL) 1β, IL6, IL8, MMP1 and MMP3. Adiponectin abrogated significantly the stimulatory effects of LPS on these molecules. Similarly, adiponectin inhibited significantly the LPS-induced decrease in cell viability and increase in cell proliferation and differentiation. Adiponectin led to a time-dependent induction of the anti-inflammatory mediators IL10 and heme oxygenase 1, and blocked the LPS-stimulated NFκB nuclear translocation. Adiponectin may counteract critical actions of P. gingivalis on oral epithelial cells. Low levels of adiponectin, as observed in obese individuals, may increase the risk for periodontal inflammation and destruction.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10−9, OR = 1.36, 95% CI = [1.23–1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10−9, OR = 1.24, 95% CI = [1.15–1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.

Hydraulic calcium silicate cements (HCSCs) are contemporary materials in vital pulp therapy (VPT) and regenerative endodontic therapy (RET) due to their favorable effects on pulpal and periodontal cells, including cell differentiation and hard tissue formation. Recent studies also indicated the involvement of several S100A proteins in inflammatory, differentiation, and mineralization processes of the pulp. The aim of the present study was to investigate the effects of HCSCs on S100A gene expression in human dental pulp stem cells (hDPSCs). Human DPSCs were isolated and characterized by multi-lineage stem-cell markers and differentiation protocols. In stimulation experiments hDPSCs were exposed to ProRoot®MTA, Biodentine®, IL-1β, and dexamethasone. Cell viability was determined by XTT assay. IL-6 and IL-8 mRNA expression was measured to analyze proinflammatory response. In addition, odontogenic differentiation and biomineralization assays were conducted (DSPP- and ALP-mRNA expression, ALP activity, and Alizarin Red staining). Differential expression of 13 S100A genes was examined using qPCR. Low concentrations of HCSCs enhanced the proliferation of hDPSCs, whereas higher concentrations exhibited cytotoxic effects. HCSCs induced a pro-inflammatory response and led to odontogenic differentiation and biomineralization. This was accompanied by significant alterations in the expression levels of various S100A genes. ProRoot®MTA and Biodentine® significantly affect the expression of several S100A genes in hDPSCs, supporting their role in inflammation, differentiation, and mineralization. These findings indicate a link between the effects of HCSCs on human pulp cells during VPT or RET and S100A proteins.

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10 −4 ), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10 −5 ) and RNASE2 (rs2771342, P = 2.84×10 −5 ) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA- DQH1 (rs9271850, P = 2.52×10 −14 ) and HLA- DPA1 (rs17214512, P = 5.14×10 −5 ). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.

The periodontal microbiota is ecologically diverse and may facilitate colonization by bacteria of enteric origin (Enterobacteriaceae, Enterococci) and co-infections with Candida albicans, possibly producing subgingival biofilms with high antimicrobial tolerance. This retrospective surveillance study followed periodontitis-associated superinfection profiles in a large patient sample. From 2008 to 2015, biofilm samples from deep periodontal pockets were collected from a total of 16,612 German adults diagnosed with periodontitis. The presence of selected Enterobacteriaceae, Enterococci, and Candida albicans was confirmed in overnight cultures. Antimicrobial susceptibility of these clinical isolates was tested by disk diffusion with antibiotics routinely used for treatment of oral infections, e.g., amoxicillin (AML), amoxicillin/clavulanic acid (AMC), doxycycline (DO), and ciprofloxacin (CIP). The mean annual prevalence of patients harboring Enterobacteriaceae in periodontal plaques was 11.5% in total and ranged from 2.5% for Enterobacter cloacae to 3.6% for Klebsiella oxytoca, 1.1% for Klebsiella pneumoniae, 2.8% for Serratia marcescens, and 1.5% for Serratia liquefaciens. In comparison, the mean detection rates for microbiota typically found in the oral cavity were higher, e.g., 5.6% for Enterococcus spp. and 21.8% for Candida albicans. Among the Enterobacteriaceae, species harboring intrinsic resistance to AML (Enterobacter spp., Klebsiella spp., Serratia spp.) were predominant. Non-susceptibility to AMC was observed for Serratia spp. and Enterobacter cloacae. By contrast, Enterococcus spp. only showed non-susceptibility to DO and CIP. Trends for increasing resistance were found to AML in Serratia liquefaciens and to DO in Enterococcus spp. Trend analysis showed decreasing resistance to AMC in Serratia liquefaciens and Klebsiella oxytoca; and to DO in Serratia marcescens, liquefaciens, and Enterobacter cloacae. This study confirms the low but consistent presence of Enterobacteriaceae and Enterococci among the subgingival microbiota recovered from periodontitis specimen. Although their pathogenetic role in periodontal lesions remains unclear, their presence in the oral cavity should be recognized as a potential reservoir for development and spread of antibiotic resistance in light of antibiotic usage in oral infections.

Back scatter interferometry (BSI) is a sensitive method for detecting changes in the bulk refractive index of a solution in a microfluidic system. Here we demonstrate that BSI can be used to directly detect enzymatic reactions and, for the first time, derive kinetic parameters. While many methods in biomedical assays rely on detectable biproducts to produce a signal, direct detection is possible if the substrate or the product exert distinct differences in their specific refractive index so that the total refractive index changes during the enzymatic reaction. In this study, both the conversion of glucose to glucose-6-phosphate, catalyzed by hexokinase, and the conversion of adenosine-triphosphate to adenosine di-phosphate and mono-phosphate, catalyzed by apyrase, were monitored by BSI. When adding hexokinase to glucose solutions containing adenosine-triphosphate, the conversion can be directly followed by BSI, which shows the increasing refractive index and a final plateau corresponding to the particular concentration. From the initial reaction velocities, KM was found to be 0.33 mM using Michaelis–Menten kinetics. The experiments with apyrase indicate that the refractive index also depends on the presence of various ions that must be taken into account when using this technique. This study clearly demonstrates that measuring changes in the refractive index can be used for the direct determination of substrate concentrations and enzyme kinetics.

Background Major incidents (MI) are rare occurrences in Scandinavia. Literature depicting Scandinavian MI management is scarce and case reports and research is called for. In 2019, a trailer falling off a freight train struck a passing high-speed train on the Great Belt Bridge in Denmark, killing eight people instantly and injuring fifteen people. We aim to describe the emergency medical services (EMS) response to this MI and evaluate adherence to guidelines to identify areas of improvement for future MI management. Case presentation Nineteen EMS units were dispatched to the incident site. Ambulances transported fifteen patients to a trauma centre after evacuation. Deceased patients were pronounced life-extinct on-scene. Radio communication was partly compromised, since 38.9% of the radio shifts were not according to the planned radio grid and presented a potential threat to patient outcome and personnel safety. Access to the incident site was challenging and delayed due to traffic congestion and safety issues. Conclusion Despite harsh weather conditions and complex logistics, the availability of EMS units was sufficient and patient treatment and evacuation was uncomplicated. Triage was relevant, but at the physicians’ discretion. Important findings were communication challenges and the consequences of difficult access to the incident site. There is a need for an expansion of capacity in formal education in MI management in Denmark.

Aim To evaluate the outcomes following surgical periodontal treatment and root surface decontamination by means of air polishing using an erythritol powder or conventional mechanical root debridement. Material and methods Thirty systemically healthy patients (44.38 ± 8.2 years old, 11 smokers, 19 women) diagnosed with periodontitis stages III–IV were included. Each patient, with one single-rooted tooth, with one probing pocket depth (PD) ≥ 6 mm associated with horizontal bone loss, was treated by means of simplified papilla preservation flap (SPPF) and randomized to either test treatment (careful removal of the calculus with the tip of a blade, air polishing of the root surfaces with erythritol) or to the control group (scaling and root planing with hand curettes, ultrasonic instruments). PD, clinical attachment (CAL), bone sounding (BS), and radiographic bone level (BL) were evaluated at baseline and 12 months postsurgically. Results Twenty-seven patients completed the 12-month follow-up (test: n = 14, control: n = 13). In both groups, statistically significant improvements were obtained ( p < 0.05, mean CAL gain/PD reduction: test, 2.50 ± 1.60 mm/3.00 ± 0.96 mm; control, 2.85 ± 1.21 mm/3.38 ± 1.12 mm). No statistically significant differences were observed between the groups for any of the investigated parameters ( p < 0.05). Conclusion Within their limits, the present results indicate that the use of air polishing with an erythritol powder during periodontal surgery may represent a valuable minimally invasive adjunct following calculus removal by means of hand and ultrasonic instruments or a valuable alternative to these, for root surfaces without calculus. Clinical relevance The use of air polishing with an erythritol powder during periodontal surgery appears to represent a valuable minimally invasive adjunct following calculus removal by means of hand and ultrasonic instruments or a valuable alternative to these, for root surfaces without calculus.

Background Between 1998 and 2015, we report on the survival of congenital diaphragmatic hernia (CDH)-infants presenting with symptoms within the first 24 h of life, treated at Odense University Hospital (OUH), a tertiary referral non-extracorporeal membrane oxygenation (ECMO) hospital for paediatric surgery. Methods We performed a retrospective cohort study of prospectively identified CDH-infants at our centre. Data from medical records and critical information systems were obtained. Baseline data included mode of delivery and infant condition. Outcome data included 24-h, 28-day, and 1 year mortality rates and management data included intensive care treatment, length of stay in the intensive care unit, time of discharge from hospital, and surgical intervention. Descriptive analyses were performed for all variables. Survivors and non-survivors were compared for baseline and treatment data. Results Ninety-five infants were identified (44% female). Of these, 77% were left-sided hernias, 52% were diagnosed prenatally, and 6.4% had concurrent malformations. The 28-day mortality rate was 21.1%, and the 1 year mortality rate was 22.1%. Of the 21 non-survivors, nine died within the first 24 h, and 10 were sufficiently stabilised to undergo surgery. A statistically significant difference was observed between survivors and non-survivors regarding APGAR score at 1 and 5 min., prenatal diagnosis, body length at birth, and delivery at OUH. Conclusions Our outcome results were comparable to published data from other centres, including centres using ECMO.

Background A criteria-based nationwide Emergency Medical Dispatch (EMD) system was recently implemented in Denmark. We described the system and studied its ability to triage patients according to the severity of their condition by analysing hospital admission and case-fatality risks. Methods This was a register-based follow-up study of all 1-1-2 calls in a 6-month period that were triaged according to the Danish Index – the new criteria-based dispatch protocol. Danish Index data were linked with hospital and vital status data from national registries. Confidence intervals (95%) for proportions with binomial data were computed using exact methods. To test for trend the Wald test was used. Results Information on level of emergency according to the Danish Index rating was available for 67,135 patients who received ambulance service. Emergency level A (urgent cases) accounted for 51.4% (n = 34,489) of patients, emergency level B for 46.3% (n = 31,116), emergency level C for 2.1% (n = 1,391) and emergency level D for 0.2% (n = 139). For emergency level A, the median time from call receipt to ambulance dispatch was 2 min 1 s, and the median time to arrival was 6 min 11 s. Data concerning admission and case fatality was available for 55,270 patients. The hospital admission risk for emergency level A patients was 64.4% (95% CI = 63.8-64.9). There was a significant trend (p < 0.001) towards lower admission risks for patients with lower levels of emergency. The case fatality risk for emergency level A patients on the same day as the 1-1-2 call was 4.4% (95% CI = 4.1-4.6). The relative case-fatality risk among emergency level A patients compared to emergency level B–D patients was 14.3 (95% CI: 11.5-18.0). Conclusion The majority of patients were assessed as Danish Index emergency level A or B. Case fatality and hospital admission risks were substantially higher for emergency level A patients than for emergency level B–D patients. Thus, the newly implemented Danish criteria-based dispatch system seems to triage patients with high risk of admission and death to the highest level of emergency. Further studies are needed to determine the degree of over- and undertriage and prognostic factors.