The Mutational Profile of Unicystic Ameloblastoma

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM (n = 39) and to compare it to conventional AM (n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence (P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis.Peer reviewe

A genomic and historical synthesis of plague in 18th century Eurasia

Plague continued to afflict Europe for more than five centuries after the Black Death. Yet, by the 17th century, the dynamics of plague had changed, leading to its slow decline in Western Europe over the subsequent 200 y, a period for which only one genome was previously available. Using a multidisciplinary approach, combining genomic and historical data, we assembled Y. pestis genomes from nine individuals covering four Eurasian sites and placed them into an historical context within the established phylogeny. CHE1 (Chechnya, Russia, 18th century) is now the latest Second Plague Pandemic genome and the first non-European sample in the post-Black Death lineage. Its placement in the phylogeny and our synthesis point toward the existence of an extra-European reservoir feeding plague into Western Europe in multiple waves. By considering socioeconomic, ecological, and climatic factors we highlight the importance of a noneurocentric approach for the discussion on Second Plague Pandemic dynamics in Europe

The Mutational Profile of Unicystic Ameloblastoma

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence ( P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis

Hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival

Chronic myeloid leukemia (CML) stem/progenitor cells (SPC) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPC maintain quiescence will help to clarify how they persist during long-term targeted treatment. We have identified a novel BCR-ABL1 protein kinase dependent pathway mediated by the up-regulation of hsa-mir183, the down-regulation of its direct target EGR1 and, as a consequence, up-regulation of E2F1. We show here that inhibition of hsa-mir183 reduced proliferation and impaired colony formation of CML SPC. Downstream of this, inhibition of E2F1 also reduced proliferation of CML SPC, leading to p53-mediated apoptosis. In addition, we demonstrate that E2F1 plays a pivotal role in regulating CML SPC proliferation status. Thus, for the first time, we highlight the mechanism of hsa-mir183/EGR1-mediated E2F1 regulation and demonstrate this axis as a novel, critical factor for CML SPC survival, offering new insights into leukemic stem cell eradication

European Society of Endodontology position statement: Management of deep caries and the exposed pulp

This position statement on the management of deep caries and the exposed pulp represents the consensus of an expert committee, convened by the European Society of Endodontology (ESE). Preserving the pulp in a healthy state with sustained vitality, preventing apical periodontitis and developing minimally invasive biologically based therapies are key themes within contemporary clinical endodontics. The aim of this statement was to summarize current best evidence on the diagnosis and classification of deep caries and caries‐induced pulpal disease, as well as indicating appropriate clinical management strategies for avoiding and treating pulp exposure in permanent teeth with deep or extremely deep caries. In presenting these findings, areas of controversy, low‐quality evidence and uncertainties are highlighted, prior to recommendations for each area of interest. A recently published review article provides more detailed information and was the basis for this position statement (Bjørndal et al. 2019, International Endodontic Journal, doi:10.1111/iej.13128). The intention of this position statement is to provide the practitioner with relevant clinical guidance in this rapidly developing area. An update will be provided within 5 years as further evidence emerges

Maxillary sinus augmentation with iliac autograft - a health-economic analysis.

PURPOSE: To estimate and compare the costs of maxillary sinus augmentation performed with autologous bone graft either from the iliac crest or from local bone harvested from the mandibula. To evaluate post-operative health-related quality-of-life parameters for patients subjected to sinus augmentation and iliac bone surgery. MATERIAL AND METHODS: The hospital records of 14 patients subjected to sinus augmentation with iliac autograft, and 14 patients treated with local autograft, were analysed with regard to costs related to surgery, hospitalization and sick leave. Post-operative health parameters were assessed with a questionnaire. RESULTS: Mean hospital costs, administration excluded, for sinus augmentation with iliac autograft was €3447. Policlinic treatment alternatives e.g. local bone autograft with or without bone substitutes, rendered costs of approximately 42% thereof. The loss of production for a worker was 41% of the total cost (€9285). With regard to health-related quality-of-life and post-operative morbidity, most of the patients had recovered 14 days after the iliac graft surgery. CONCLUSION: The cost for a sinus augmentation with iliac surgery exceeds that of a policlinic procedure manifold. Provided that a policlinic operation with local bone, with or without bone substitute, renders an adequate end result, the economic gain would be substantial and post-operative morbidity would be greatly reduced