Caries classification and management in the context of the CariesCare International (CCI™) consensus:a clinical case study

The objective of this clinical case study is to illustrate the caries management four-step structured process, leading to personalised interventions specifc for each individual patient’s risks and needs, according to CariesCare International, derived from the International Caries Classifcation and Management System (ICCMS) for clinical practice. An 18-year-old female was diagnosed with higher caries risk at the individual level, and with several caries lesions at different severity stages, some likely active and others likely inactive. A care plan was co-created with the patient and delivered to obtain optimal health outcomes. Several issues pertinent to patient-centred care are discussed, including caries management at the individual and the tooth surface level, the preservation of tooth structure, patient’s caries risk management, and prevention and control of caries lesions. The patient’s perspective is taken into account and the health outcome focus of the system is highlighted

Evaluación de un programa de cambio de actitudes con preconductores para prevenir los accidentes de tráfico provocados por el alcohol en Cataluña

En este estudio se presentan los resultados de una intervención para prevenir el consumo de alcohol en la conducción con preconductores de todo Cataluña. El programa que se aplicó, fundamentado en el cambio de actitudes, pretende reducir considerablemente el peligro que conlleva mezclar el alcohol con la conducción. Para ello se utilizó un diseño clásico cuasi experimental pretest-posttest con grupo control y se aplicaron dos cuestionarios (uno general, con varios factores de riesgo, y otro específico sobre alcohol). El estudio se llevó a cabo con tres grupos: a) experimental 1, que recibió la aplicación completa del programa, b) experimental 2, que recibió la aplicación de una parte del mismo y c) control, que no recibió los beneficios del programa de reducción del consumo de alcohol. Se constató, a partir del análisis factorial (ACP) del cuestionario específico y de la prueba ANOVA de medidas repetidas, que el grupo experimental 1 presentaba resultados significativamente mejores que los grupos experimental 2 y control, hallándose diferencias significativas entre los hombres y mujeres de la muestra. Los resultados permiten evidenciar que el programa de cambio de actitudes resulta eficaz y que es posible reducir el consumo de alcohol en jóvenes preconductoresThis study appraises the results of an intervention to prevent drinkdriving in a cohort of pre-drivers in the region of Catalonia (Spain). The program applied, based on attitude change, sets out to reduce significantly the risk of being involved in drink-driving. A classic quasiexperimental pretest-posttest design with control group was used, and two questionnaires were applied: a general one measuring several risk factors, and another one specifically addressing the question of alcohol. The study was carried out with three groups: a) experimental 1, which received the entire program, b) experimental 2, which received a part of the program, and c) control, which did not receive the benefits of the program. Results from the factor analysis (PCA) and the repeatedmeasures ANOVA suggest that young pre-drivers who received the program obtained better results in road safety and showed less risk of drink-driving than those who did not receive the program or received only part of it. Significant differences were also found between men and women. The results confirm the effectiveness of the attitude-change program and the possibility of reducing alcohol use among young predriver

Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Antiviral resistance; Solid organ transplant; Next-generation sequencingResistencia a los antivirales; Trasplante de órganos sólidos; Secuenciación de próxima generaciónResistència als antivirals; Trasplantament d'òrgans sòlids; Seqüenciació de pròxima generacióOBJETIVES: The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. METHODS: Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. RESULTS: Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). CONCLUSIONS: NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.The present study was funded by Agency for Health Technology Assessment and Research and Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (PS12/02131 and PI17/02150) and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, FI-DGR 2017, Grant No. 00794), which is supported by the Secretaria d'Universitats i Recerca (Economy and Knowledge Department, Generalitat de Catalunya), and co-funded by the European Social Fund and by Fundacio Marato TV3 project (201824). The study sponsor had no role in the collection, analysis, or interpretation of the data

ETV5 transcription program links BDNF and promotion of EMT at invasive front of endometrial carcinomas

Myometrial infiltration represents a main clinical determinant of endometrial carcinomas (EC) presenting as aggressive high-grade deeply invasive neoplasms, substantially associated with risk of recurrence and death. The up-regulation of ETV5 transcription factor linked to the promotion of epithelial to mesenchymal transition is considered as a basic mechanism underlying the initial steps of EC invasion. In this work, we aimed to investigate the transcription program of tumor invasion regulated by ETV5. We performed a comparative Chip-on-chip analysis at invasive front and superficial area of human EC. ETV5 specific binding to promoter regions of genes related to cellular migration, adhesion and invasion at deep invasion tumor areas highlighted the relevance of neural networks associated with cellular plasticity. Interestingly, brain-derived neurotrophic factor (BDNF) demonstrated a principal role orchestrating ETV5-mediated epithelial-to-mesenchymal transition in endometrial cancer. Impairment of the BDNF/tropomyosin-related kinase B (TrkB)/extracellular signal-regulated kinase axis in endometrial cancer cell lines reversed the aggressive and invasive phenotype promoted by the up-regulation of ETV5 at the invasive front of EC. Likewise, BDNF directly impacted on the efficiency of ETV5 promoted metastasis in a mice model of endometrial distant dissemination. These results translate the recognized role of BDNF/TrkB on neural plasticity into a relevant cancer metastasis event; suggest common mechanisms shared by neural development and tumor invasion; and offer new therapeutic opportunities specifically directed against disseminated disease in endometrial cancer

An inducible knockout mouse to model the cellautonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifeninducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors

Development of a sequential workflow based on LC-PRM for the verification of endometrial cancer protein biomarkers in uterine aspirate samples

Altres ajuts: The present work has been also funded by the "Fonds National de la Recherche du Luxembourg" (FNR) via the PEARL-CPIL program to BD, and an AFR grant to AL (PDR 2013-2, Project Reference 6835664). The authors would like to acknowledge the work of all clinicians that have participated in the recruitment of clinical samples. We thank the patients for their willingness to participate in the study.About 30% of endometrial cancer (EC) patients are diagnosed at an advanced stage of the disease, which is associated with a drastic decrease in the 5-year survival rate. The identification of biomarkers in uterine aspirate samples, which are collected by a minimally invasive procedure, would improve early diagnosis of EC. We present a sequential workflow to select from a list of potential EC biomarkers, those which are the most promising to enter a validation study. After the elimination of confounding contributions by residual blood proteins, 52 potential biomarkers were analyzed in uterine aspirates from 20 EC patients and 18 non-EC controls by a high-resolution accurate mass spectrometer operated in parallel reaction monitoring mode. The differential abundance of 26 biomarkers was observed, and among them ten proteins showed a high sensitivity and specificity (AUC > 0.9). The study demonstrates that uterine aspirates are valuable samples for EC protein biomarkers screening. It also illustrates the importance of a biomarker verification phase to fill the gap between discovery and validation studies and highlights the benefits of high resolution mass spectrometry for this purpose. The proteins verified in this study have an increased likelihood to become a clinical assay after a subsequent validation phase

A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination

Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a patient-derived tissue macroarray and mRNA expression analysis, we observed high CXCR4 levels in high-grade serous epithelial ovarian carcinomas, the most metastatic tumor, compared with those in endometrioid carcinomas. CXCR4 inhibition by treatment with the CXCR4 antagonist AMD3100 or by expression of shRNA anti-CXCR4 similarly inhibited angiogenesis in several models of ovarian carcinomas orthotopically grown in nude mice, but the effect on tumor growth was correlated with the levels of CXCR4 expression. Moreover, CXCR4 inhibition completely blocked dissemination and metastasis. This effect was associated with reduced levels of active Src, active ERKs, the inhibition of EMT transition, and block of hematogenous ovarian cancer dissemination decreasing circulating human tumoral cells (CTC). In tumors, CXCR4-expressing cells also had more mesenchymal characteristics. In conclusion, our results indicate that CXCR4 expression confers a proinvasive phenotype to ovarian carcinoma cells. Thus, anti-CXCR4 therapy is a possible agent for a complementary treatment of advanced disseminated epithelial high-grade serous ovarian cancer patients