Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy:A retrospective cohort study

Objectives:Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methods: This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60–70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. Results: The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p &lt; 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. Conclusion: Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.</p

The Importance of Connexin 43 in Enamel Development and Mineralization

During enamel development, formation of hydroxyapatite crystals and regulation of pH in the enamel matrix require massive transport of ions. Both ameloblasts and adjacent dental epithelial cells in the stellate reticulum co-express several transmembrane cotransporters/ion-exchangers for transport of ions across plasma membranes. Gap junctions (GJs) enable intercellular exchanges of ions between neighboring cells. This suggests that the ameloblasts and other cell layers of the enamel organ, form a functional unit. During the bell stage of tooth formation, the non-ameloblast dental epithelium highly expresses the Na-K-Cl cotransporter (Nkcc1). Nkcc1-null mice are associated with enamel hypomineralization and increased expression of GJ protein connexin 43 (Cx43), suggesting that reduced ion transport in the Nkcc1-null mouse is in part compensated by increased intercellular ion transport through GJs. To understand the role of GJs in ion transport and its effect on pH regulation, we examined in a mouse strain in which Cx43 was ablated selectively in DMP1 expressing cells (Cx43flox/flox mice crossed with DMP1-8kb-Cre mice), including ameloblasts. Micro-CT analysis showed that the mineral density at late maturation stage incisal enamel of the Cx43-null mice was 10% less than in controls, whereas that in dentin was unchanged. Maturation stage ameloblasts of mice lacking the pH regulating sodium/bicarbonate transporter NBCe1 (Nbce1-null), or chloride channel Cftr (Cftr-null) were found to have increased Cx43-immunostaining. These results support the possibility that GJs in the ameloblast–papillary complex at the maturation stage contribute to ion transport by enabling passage of ions directly from cells of the papillary layer into ameloblast layer. Increasing the number of GJs may partly compensate the reduction of ion-cotransporters and ion exchangers in dental epithelium

Surgical treatment of fractures of the zygomaticomaxillary complex: effect of fixation on repositioning and stability. A systematic review

Management of zygomaticomaxillary complex (ZMC) fractures can be challenging. Consequently, there is a difference in treatment amongst clinicians. In the literature it remains unclear if the number of fixation points affects the quality of the anatomical reduction, stability through time, and potential complications. Therefore, the objective of this study was to assess the outcome of no fixation, one-point fixation and multiple-point fixation of ZMC fractures. MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials were searched to identify eligible studies. After screening 925 articles, 17 studies fulfilled the inclusion criteria. Based on this systematic review no clear conclusions can be drawn on how stability, repositioning, and postoperative complications are affected by the number of fixation points. Nevertheless, it can be concluded that the advantage of multiple approaches is direct visualisation, and the downside is potentially approach-related complications. This review suggests that intraoperatively assisted cone-beam computed tomography (CBCT) can help improve the quality of the repositioning and by minimising the number of fixation points, the number of postoperative complications could be further reduced

Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy:A retrospective cohort study

Objectives:Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methods: This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60–70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. Results: The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p &lt; 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. Conclusion: Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.</p

Taste and smell disturbances in patients with chronic oral graft vs. host disease: An observational study

BACKGROUND: A common complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) is chronic oral graft vs. host disease (cGvHD). Oral cGvHD may present as mucosal lesions, salivary gland dysfunction, and trismus. Moreover, taste and smell ability may be affected, but the prevalence, nature and severity of altered taste and smell function, and their impact on quality of life (QoL) are understudied. AIM: To identify the prevalence, nature, and severity of taste and smell disturbances, their impact on QoL and to assess whether altered taste/smell ability is associated with oral mucosal cGvHD or hyposalivation. MATERIALS AND METHODS: AlloHSCT recipients at least 100 days post-HSCT and referred for oral cGvHD-related oral complaints were eligible for participation in this cross-sectional study. Manifestations of oral mucosal cGvHD were scored, the (un)stimulated salivary flow was measured, and objective taste and smell ability was evaluated. Subjective taste and smell alterations, and overall and oral health (OH)-related QoL were assessed. RESULTS: In total, 45 patients were included, of which objective reduced taste ability (hypogeusia) was identified in 68.9%; 28.9% had reduced smell ability and 11.1% had complete loss of smell. Nevertheless, only 31.1% of patients reported severe taste alterations and 22% reported moderate taste alterations indicating that not all the patients were aware of their altered taste sense. Taste/smell disturbances were not related to oral mucosal cGvHD or hyposalivation. Most alloHSCT recipients reported a decreased OH-related QoL. However, a relation between taste/smell ability and global or OH-related QoL could not be identified. CONCLUSION: Taste and smell disturbances are prevalent among alloHSCT recipients. Most patients reported a decreased OH-related QoL, but the specific impact of taste and smell disturbances remains to be elucidated

Candida and Porphyromonas gingivalis: the effect on wound closure in vitro

Microorganisms play a role in oral mucositis after cancer therapy. The current study explored the hypothesis that Candida spp. alone and together with Porphyromonas gingivalis cause delayed healing of oral ulcerations due to the inhibition of wound closure. An in vitro scratch assay model was used to study the influence of viable and heat-killed Candida glabrata, Candida kefyr, and Candida albicans on cell migration of oral epithelial cells. Separately, the effect of conditioned medium of Candida spp. and the effect of a mixed infection of Candida spp. with P. gingivalis on wound closure was studied. In the presence of 10 viable C. glabrata or C. kefyr versus one epithelial cell, with a multiplicity of infection (MOI) of 10, the relative closure of the scratch was 26% and 17%, respectively. At a MOI of 1, this was 60% for C. glabrata and 78% for C. kefyr. The inhibition of oral epithelial cell migration challenged with either C. glabrata or C. kefyr together with P. gingivalis was stronger than the inhibition caused by one of both organisms separately. Candida spp. inhibit cell migration in vitro. A combination of Candida spp. and P. gingivalis inhibited cell migration more than either microorganism separatel

Effect of nutritional supplementation in the development of native forest species of Cerrado in nursery

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Florestal, 2017.A exploração desordenada dos recursos naturais tem gerado a degradação de áreas em quase todo o território nacional, promovendo o aumento da demanda por produtos e serviços voltados à recuperação de áreas degradadas e, ou, perturbadas, em especial para produção de mudas de espécies florestais nativas. O presente trabalho teve como objetivo avaliar o efeito da fertilização do substrato e da suplementação nutricional via folha sobre o desenvolvimento de mudas de espécies florestais nativas do Cerrado em condições de viveiro, Kielmeyera coriacea Mart. & Zucc., Eugenia dysenterica (Mart.) DC., Handroanthus impetiginosus (Mart. ex DC.) Mattos e Myracrodruon urundeuva Allemão. O experimento foi implantado utilizando-se delineamento inteiramente casualizado (DIC), em esquema fatorial com dois fatores: o substrato em três níveis e a adubação foliar em três níveis, com dez repetições. Foram avaliados três tipos de substratos: 1 - Terra (Latossolo vermelho); 2 - Terra + esterco bovino na proporção 2:1; 3 - Terra + esterco bovino na proporção 2:1 + 2,2 Kg de NPK (10-10-10) por metro cúbico de substrato + 1,3 kg de calcário por metro cúbico de substrato. Tais substratos foram associados às três doses de adubação suplementar foliar (NPK aplicado semanalmente; NPK aplicado trimestralmente; e testemunha, sem aplicação de NPK foliar). Os tratamentos foram submetidos a análise de variância, avaliando os incrementos de altura, diâmetro e índice de qualidade de Dickson. Para a espécie Pau Santo é recomendado utilizar substrato composto apenas por Latossolo Vermelho, já para as espécies Cagaita e Ipê Roxo é recomendado utilizar substrato composto por Latossolo Vermelho com adição de esterco bovino na razão 2:1, não sendo recomendado realizar a adubação via foliar na produção de mudas para todas as espécies estudadas. A Aroeira não foi inserida nas análises, pois teve a incidência de “Tripes” nos primeiros meses pós transplantio, tendo seu crescimento prejudicado. Quanto a análise de solo, a matéria orgânica, quantidade de fósforo e cálcio foram determinantes na formação de grupos por meio da análise de componentes principais. A correlação das variáveis químicas do substrato não foi capaz de explicar com precisão as variáveis de medição e a distribuição das espécies em cada substrato no gradiente, por meio da análise de correspondência canônica.The Disorganized exploration of natural resources has led to the degradation of areas in most of the national territory, thus increasing the demand for products and services aimed at the recovery of degraded land and, especially, for the production of native forest species seedlings. The objective of this study was evaluate the effect of substrate fertilization and leaf nutritional supplementation on the development of seedlings of native Cerrado forest species in nursery conditions, Pau Santo (Kielmeyera coriacea Mart. & Zucc.), Cagaita Eugenia dysenterica (Mart.) DC.), Ipê Roxo (Handroanthus impetiginosus (Mart. Ex DC.) Mattos) and Aroeira (Myracrodruon urundeuva Allemão). The experiment was implemented using a completely randomized design (CRD), in a factorial scheme with two factors: the substrate with three levels and foliar fertilization with three levels, with ten replicates. Three types of substrates were evaluated: 1 - Land (Red Latosol); 2 - Land + bovine manure in the proportion of 2:1; 3 - Land + bovine manure in a ratio of 2:1 + 2.2 kg NPK (10-10-10) per cubic meter of substrate + 1.3 kg of limestone per cubic meter of substrate. These substrates were associated with three doses of foliar fertilization (NPK applied weekly, NPK applied quarterly, and control, without foliar NPK application). The treatments were submitted to analysis of variance, evaluating Dickson, height, diameter and quality index increments. For Pau Santo species, it is recommended to use a substrate composed only of red latosol, and for the species Cagaita and Ipê Roxo it is recommended to use a substrate composed of Red Latosol with addition of bovine manure in the proportion of 2:1 ratio, and it is not recommended to apply foliar fertilization In the production of seedlings for all species studied. Aroeira was not included in the analyzes, as it had the incidence of Tripes in the first months after transplanting, and its growth was impaired. Regarding soil analysis, organic matter, amount of phosphorus and calcium were determinants in the formation of groups by principal component analysis. The correlation of the substrate chemical variables was not able to accurately explain the measurement variables and the distribution of the species in each substrate in the gradient by canonical correspondence analysis

Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activity and reproductive capacity of epithelial cells in vitro

Purpose: Clinical and in vitro studies showed selected oral microorganisms to be related to delayed wound healing and ulcerative oral mucositis. However, it is not known whether this effect is due to reduced metabolism and/or the reduced reproductive capacity of epithelial cells. Therefore, we studied the influence of the oral microorganisms Porphyromonas gingivalis, Candida glabrata, and Candida kefyr on cell metabolism and reproductive capacity of oral epithelial cells, aimed to further unravel the pathogenesis of oral mucositis. Methods: Oral epithelial cells were exposed to different concentrations of P. gingivalis, C. glabrata, and C. kefyr as mono-infections or mixed together. An MTT assay was performed to determine the effect on cell metabolism. A clonogenic assay was used to study the effect on the reproductive capacity of oral epithelial cells. Results: The metabolism of oral epithelial cells was reduced when the microorganisms were present in high concentrations: P. gingivalis at a multiplicity of infection (MOI) of 1000 and the Candida spp. at MOI 100. No statistical difference was observed in the ability of a single epithelial cell to grow into a colony of cells between control and P. gingivalis, C. glabrata, and C. kefyr, independent of the concentrations and combinations used. Conclusion: P. gingivalis, C. glabrata, and C. kefyr lowered the metabolic activity of oral epithelial cells in high concentrations, yet they did not influence the reproductive capacity of epithelial cells. Their impact on ulcerative oral mucositis is likely due to an effect on the migration, proliferation, and metabolism of epithelial cells

Tooth Formation as Experimental Model to Study Chemotherapy on Tissue Development: Effect of a Specific Dose of Temozolomide/Veliparib

Background: Chemotherapy treatment of cancer in children can influence formation of normal tissues, leading to irreversible changes in their structure and function. Tooth formation is susceptible to several types of chemotherapy that induce irreversible changes in the structure of enamel, dentin and dental root morphology. These changes can make the teeth more prone to fracture or to caries when they have erupted. Recent studies report successful treatment of brain tumors with the alkylating drug temozolomide (TMZ) in combination with veliparib (VLP) in a glioblastoma in vivo mouse model. Whether these drugs also affect tooth formation is unknown. Aim: In this study the effect of TMZ/VLP on incisor formation was investigated in tissue sections of jaws from mice and compared with mice not treated with these drugs. Materials and method: The following aspects were studied using immunohistochemistry of specific protein markers including: (1) proliferation (by protein expression of proliferation marker Ki67) (2) a protein involved in paracellular ion transport (expression of tight junction (TJ) protein claudin-1) and (3) in transcellular passage of ions across the dental epithelium (expression of Na+, K+ 2Cl-cotransporter/NKCC1). Results: Chemotherapy with TMZ/VLP strongly reduced immunostaining for claudin-1 in distal parts of maturation ameloblasts. No gross changes were found in the treated mice, either in cell proliferation in the dental epithelium at the cervical loop or in the immunostaining pattern for NKCC1 in (non-ameloblastic) dental epithelium. The salivary glands in the treated mice contained strongly reduced immunostaining for NKCC1 in the basolateral membranes of acinar cells. Discussion/Conclusions: Based on the reduction of claudin-1 immunostaining in ameloblasts, TMZ/VLP may potentially influence forming enamel by changes in the structure of TJs structures in maturation ameloblasts, structures that are crucial for the selective passage of ions through the intercellular space between neighboring ameloblasts. The strongly reduced basolateral NKCC1 staining seen in fully-grown salivary glands of TMZ/VLP-treated mice suggests that TMZ/VLF could also influence ion transport in adult saliva by the salivary gland epithelium. This may cause treated children to be more susceptible to caries