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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. It is a result of numerous aetiological factors such as genetic predisposition, smoking, excessive alcohol consumption and viruses such as the human papilloma virus. Due to late diagnosis it has a high mortality and morbidity rates which has remained unchanged over the last 5 decades. Currently no screening is available for high risk patients for better monitoring. Diagnosing OSCC relies on histopathology of biopsy tissue, reviewed for dysplasia and advancing lesions. Although the technique has been used for decades for successful diagnosis it fails to identify the molecular signature of OSCC which appears much before the visual signs. It also falls short in predicting the malignant transformation of pre-malignant oral lesions. Identifying the molecular and genetic changes leading to OSCC lesion will aid in more specific (quantitative) and early diagnosis of the disease reducing the financial burden of treating late-stage OSCC patients on the healthcare system. This study focuses on developing new adjuncts which can be used alongside histopathology for early diagnosis. There is a need to monitor high risk patients through non-invasive methods causing less patient discomfort. We therefore explored the potentials of exosomes which are extracellular vesicles secreted by normal and tumour cells. They can be isolated from body fluids such as blood and saliva. In cancer biology exosomes offer both diagnostic and therapeutic advantage. Their involvement in cell-cell communication indicates their influence in tumour development, progression, metastasis and therapeutic efficacy. Exosomes released by cancerous cells carry numerous biomarkers, which are passed on to healthy cells via microenvironment, causing stromal and angiogenic activation along with immune escape. In this study exosomes were successfully isolated from body fluids (blood, saliva and plasma) and cell line supernatant through ultracentrifugation and characterised by visual and particle size quantification techniques including Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), Zetasizer and Nanosight Tracking Analysis (NTA). Exosomal specific membrane proteins were identified through Western blotting. 5 We report the presence of a potential protein biomarker located exclusively on the outer membrane of cancer exosomes. Since body fluids consist of a heterogeneous population of exosomes derived from multiple cell types, such surface biomarker can potentially be used to isolate OSCC exosomes. Characterisation of exosomal mRNA cargo was done using Agilent Bioanalyzer (for RNA quantity and quality assurance) and reverse transcription-quantitative PCR (RT-qPCR; for gene specific quantitation). Functional significance of exosomes was studied by transfecting normal oral keratinocyte cells with self and cancer-derived exosomes. Through gene-expression microarray and subsequent RT-qPCR verification, we report a panel of differentially expressed genes involved in essential cellular functions being modulated by exosome transfection. A previously developed molecular diagnostic system by our research group called quantitative malignancy index diagnostic system (qMIDS) based on FOXM1 oncogene and its downstream targets was validated on archival formalin fixed paraffin embedded OSCC patient biopsy samples. We report that qMIDS index successfully correlates with the disease stages including dysplasia, tumour and lymph node metastasis. Furthermore, through meta-analysis of 8 OSCC microarray studies we identified a panel of six genes including PLAU, FN1, CDCA5, CRNN, CLEC3B and DUOX1 (q6) which are able to identify two clinically distinct sub-groups of OSCC patient population. Through RT-qPCR the expression of q6 biomarkers was established in 100 OSCC biopsy samples. This information can be of immense importance in developing personalized treatment strategies based on the molecular makeup of the presenting tumour.

O Diabetes mellitus gestacional (DMG) é uma séria condição que afeta muitas gestantes e traz muitos riscos tanto para a gestante, como para o feto. A recomendação é que se faça o rastreamento com teste oral de tolerância à glicose (TOTG) entre 24 e 28 semanas de gestação. O objetivo desse estudo é determinar a utilidade do teste de hemoglobina glicada (A1c) como teste diagnóstico de DMG, comparado com os critérios baseados na medida de glicemia. Métodos: este é um estudo de acurácia de teste diagnóstico. Nós avaliamos o metabolismo dos carboidratos através dos testes de TOTG e A1c em mulheres grávidas brasileiras atendidas nas visitas de pré-natal do Hospital de Clínicas de Porto Alegre (HCPA). Além dos testes de TOTG e A1c, foi analisada a história clínica das pacientes. O DMG foi definido de acordo com critério da American Diabetes Association (ADA) - um ou mais pontos alterados, glicemia de jejum, 1h ou 2h com concentrações de glicose plasmática ≥5.1, 10.0, ou 8.5 mmol/L, respectivamente-, ou de acordo com os critérios da Organização Mundial da Saúde (OMS) - glicemia de jejum ou 2h com concentrações de glicose plasmática ≥7.0mmol/L ou ≥7.8mmol/L, respectivamente. Presença de anemia, hemoglobinas variantes e doença renal crônica foram excluídas. Para avaliar o desempenho do teste de A1c foi utilizada a curva ROC (receiver operating characteristic curve). Resultados: um total de 262 mulheres grávidas (média de idade de 30 anos, média de idade gestacional de 26 semanas) foram avaliadas e 82 (31,3%) tiveram diagnóstico positivo (40 pelo critério da ADA e 42 pelo critério da OMS). Baseado na análise da curva ROC, considerando os critérios da ADA e OMS juntos e o TOTG como teste de referência, o ponto de corte para obter o melhor equilíbrio entre sensibilidade e especificidade (diagonal 100% a 100%) foi o valor de A1c de 31mmol/mol (5,3%). A sensibilidade e especificidade para este ponto de corte foi de 69,9% e 65,9%, respectivamente. Os pontos de corte de 40 mmol/mol (5.8%), 41 mmol⁄mol (5.9%) e 42 mmol⁄mol (6.0%) representaram especificidades de 96,1%, 96,6% e 98,3%, respectivamente. Conclusões: o teste de A1c apresenta baixa sensibilidade e alta especificidade para o diagnóstico de DMG, quando comparado com o critério tradicional. Nossos resultados mostraram que 39% dos casos de DMG foram diagnosticados usando o ponto de corte de A1c≥ 40 mmol/mol (5.8%). O teste de A1c, sozinho ou em combinação com o TOTG, talvez seja bastante útil no diagnóstico de DMG. / BACKGROUND: Gestational diabetes mellitus (GDM) is a potentially serious condition that affects many pregnancies and it carries risk for the mother and neonate. The current recommendation is to perform screening before 24 - 28 weeks of gestation by an oral glucose tolerance test (OGTT). The aim of this study is to determine the usefulness of glycated hemoglobin (A1c) as a diagnostic tool for GDM compared with the traditional criteria based on glycemia measurements. METHODS: This is a study of diagnostic test accuracy. We evaluated the status of carbohydrate metabolism by performing OGTT and A1c in Brazilian pregnant women attending prenatal visits at Hospital de Clínicas de Porto Alegre (HCPA). A1c, OGTT, and clinical history were analyzed. GDM was defined according to the American Diabetes Association (ADA) criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations ≥5.1, 10.0, or 8.5 mmol/L; respectively) or World Health Organization (WHO) criteria (fasting or 2-h plasma glucose ≥7.0mmol/L or ≥7.8mmol/L, respectively). Presence of anemia, variant hemoglobins and chronic renal disease were excluded. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of A1c. RESULTS: A total of 262 pregnant women (mean age 30 years, mean gestational duration 26 weeks) were enrolled and 82 (31.3%) were diagnosed with diabetes (40 by ADA criteria and 42 by WHO criteria). Based on ROC curve analysis, and considering OGTT as the reference criterion, the cut-off point obtained by the point with the best equilibrium between sensitivity and specificity (100%-to-100% diagonal) was A1c value of 31 mmol⁄mol (5.3%). The sensitivity and specificity for this cut-off 27 point were 69.9 % and 65.9 %, respectively. The cut-off points of A1c of 40 mmol/mol (5.8%), 41 mmol⁄mol (5.9%) and 42 mmol⁄mol (6.0%) presented specificities of 96,1%, 96,6% and 98,3%, respectively. CONCLUSIONS: A1c test presented low sensitivity and very high specificity for GDM diagnosis when compared with traditional criteria. Our results show that 39% of GDM cases would be diagnosed by using the cut-off point A1c≥ 40 mmol/mol (5.8%) alone. A1c test, alone or in combination with OGTT, may be a very useful diagnostic tool in GDM.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Physics, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 190-193. / by Bruce Robert Rosen. / M.S.

Zhang Jun. / "August 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 109-144). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

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O pilar do sucesso do tratamento endodôntico é o diagnóstico e, para esse objetivo, a radiografia é um excelente recurso auxiliar, tanto pelo seu custo, como pela facilidade de obtenção. Contudo, ela tem suas limitações, pois trata-se da imagem bidimensional de um objeto tridimensional e daí a dificuldade encontrada no diagnóstico de lesões periapicais, fraturas radiculares e reabsorções dentais. Com o advento e o uso da tomografia computadorizada (TC), a partir de 1972, houve uma melhora na capacidade diagnóstica, com as imagens tridimensionais. Entretanto, a TC helicoidal tem limitações, na Odontologia, pelo seu custo, alta dose de radiação à qual o paciente é submetido pela presença de artefatos metálicos. Com a introdução da tomografia computadorizada na Odontologia, por meio do sistema de aquisição Cone Beam, essas desvantagens foram minimizadas, ocorrendo o aumento da qualidade diagnóstica da imagem tridimensional. O objetivo deste trabalho foi comparar a capacidade diagnóstica da tomografia computadorizada Cone Beam, utilizando o aparelho Accuitomo 3DX com as radiografias periapicais e ortopantomográficas (panorâmicas), em casos de lesões periapicais, fraturas radiculares e reabsorções dentais. Para isso, foram analisadas imagens obtidas por meio da tomografia e pelas técnicas radiográficas periapical e panorâmica de 150 casos clínicos, por dois examinadores calibrados, usando escores préestabelecidos. Os resultados permitiram afirmar que a técnica da tomografia apresentou diferença estatisticamente significante em relação às demais técnicas, no diagnóstico da extensão e localização de lesões periapicais, fraturas radiculares e reabsorções dentais. / Diagnosis is the basis of success of endodontic treatment; radiography is an excellent aid for that purpose, due to both cost and easy achievement. However, it also has limitations, since it is a bidimensional image of a three-dimensional object; this explains the difficulty in the diagnosis of periapical lesions, root fractures and tooth resorptions. The advent and use of computerized tomography (CT) since 1972 improved the diagnostic ability with utilization of three-dimensional images. However, helical CT is limited in Dentistry, due to its cost, high radiation dose and presence of metallic artifacts. These disadvantages were minimized by introduction of the cone beam system in dentistry, which improved the diagnostic quality of three-dimensional images. This study evaluated the diagnostic ability of cone beam computerized tomography using the appliance Accuitomo 3DX, compared to periapical and panoramic radiographs, in cases of periapical lesions, root fractures and tooth resorptions. Images of 150 clinical cases were obtained by tomography and by periapical and panoramic radiographic techniques and evaluated by two calibrated examiners, using pre-established scores. The results revealed that the tomography technique presented statistically significant difference in relation to the other techniques for diagnosis of the extent and location of periapical lesions, root fractures and tooth resorptions.

Durante o século passado, o diagnóstico por imagem na odontologia, foi dominado por radiografias, que são representações bidimensionais de estruturas tridimensionais, com sobreposição e distorções associadas. Com a introdução da tomografia computadorizada cone-beam (TCCB), houve um aumento no interesse por esta tecnologia dado às vantagens, como melhor qualidade de imagem, reconstrução tridimensional, possibilidade de visualização craniofacial, e as doses de radiação mais baixas em comparação com a tomografia computadorizada convencional (TC). A TCCB pode ser aplicada em diversas áreas da Odontologia, tais como: implantodontia, cirurgia, traumatologia, periodontia, endodontia, ortodontia, articulações temporomandibulares. Contudo, os profissionais da saúde devem estar cientes que os avanços tecnológicos terão implicações importantes sobre a prática clínica. Estes mesmos profissionais devem conhecer as indicações, limitações e implicações antes de considerar a utilização de tal equipamento. Sendo assim, o presente estudo pretende analisar, criticamente, a utilização e indicação do exame de imagem TCCB na Faculdade de Odontologia de Bauru USP. Ao mesmo tempo, pretende avaliar quantitativamente o uso deste equipamento em relação ao motivo da solicitação e a área bucal requisitada. / During the past century, the diagnostic for image in the dentistry, was dominated for radiographies, which are bidimensional representation of the tridimensional structure with superposition and distortion associated. With the introduction of cone-beam computed tomography (TCCB), there was an increased interest in this technology due to advantages such as better image quality, three-dimensional reconstruction, ability of craniofacial visualization and lower radiation doses compared with the conventional computed tomography (CT). The TCCB can be applied in various areas of dentistry such as dental implants, surgery, traumatology, periodontics, endodontics, orthodontics, temporomandibular joints. However, health professionals should be aware that technological advances have important implications for clinical practice. These same professionals should know the indications, limitations and implications before considering the use of such equipment. Thus, this study aims to analyze critically the use and indication of imaging examination TCCB in the Bauru Dental School - USP. At the same time, evaluate quantitatively the use of equipment for the purpose of the request.

Esta pesquisa foi realizada com o objetivo de identificar as inclinações dentárias vestíbulo-linguais dos dentes superiores e inferiores e as espessuras ósseas alveolares maxilo-mandibulares em indivíduos com deformidade dentofacial de classe III e comparar com indivíduos com oclusão normal para verificar, a partir da correlação entre estas duas variáveis, se o processo natural de remodelação óssea provê uniformidade da espessura óssea, ou se a mesma varia em torno das raízes em função da inclinação dentária. A amostra constituiu-se de 70 indivíduos adultos, 35 com face equilibrada e oclusão normal, e 35 com deformidade dentofacial de classe III, não tratados ortodonticamente e com saúde periodontal. A partir de imagens tridimensionais geradas por exames de tomografia computadorizada de feixe cônico, foram mensuradas as inclinações vestíbulo-linguais de todos elementos dentários e as espessuras ósseas alveolares maxilo-mandibulares em três alturas diferentes (3, 6 e 8 milímetros) a partir da junção amelocementária por meio do programa Dolphin 3D®. O erro do método foi avaliado por meio das correlações intraclasses e pela fórmula de Dahlberg. O teste de Correlação de Pearson foi utilizado para verificar a relação entre inclinação dentária e espessura óssea. As espessuras médias nas alturas de 3 e 8 milímetros e as inclinações foram comparadas entre os dois grupos com uso de testes t-Student. As medidas apresentaram alta reprodutibilidade. A região alveolar correspondente ao canino superior apresentou-se mais delgada e a palatina dos incisivos centrais superiores mais espessa. Na mandíbula, as maiores medidas de espessura óssea alveolar foram observadas na região disto-vestibular do segundo molar inferior. Os dados observados mostram valores menores das medidas avaliadas na altura de 3 mm da junção amelocementária, para ambos grupos estudados. Nos indivíduos com oclusão normal, as maiores inclinações foram observadas nos incisivos e estes valores foram diminuindo progressivamente em direção posterior. Nos indivíduos com deformidades dentofaciais de classe III, as maiores inclinações foram observadas nos incisivos superiores e nos caninos inferiores e as menores inclinações foram observadas nas raízes vestibulares dos segundos molares inferiores. Em relação à comparação entre os grupos estudados, os segundos prémolares, incisivos laterais e os incisivos centrais superiores apresentaram maiores inclinações e os segundos molares, primeiros pré-molares e incisivos laterais e centrais inferiores apresentaram-se menos inclinados nos indivíduos classe III. Todas as espessuras médias em 3 mm foram estatisticamente menores nos indivíduos classe III em relação aos indivíduos com oclusão normal, e a maioria das espessuras avaliadas em 8 mm apresentou menor valor nos indivíduos classe III. Além disso, nos indivíduos classe III, foram encontradas mais correlações estatisticamente significativas positivas entre inclinação e espessura nos dentes inferiores, enquanto que nos indivíduos com oclusão normal, foram encontradas poucas correlações estatisticamente significativas entre estas duas variáveis. / This research was conducted with the purposes of identifying the buccolingual inclinations of the upper and lower teeth and the maxillo-mandibular alveolar bone thickness in patients with Class III dentofacial deformities and of comparing these measurements with those from individuals with normal occlusions to verify, based on the correlation between these two variables, whether the natural process of bone remodeling provides uniformity of bone thickness or whether it varies around the roots due to tooth inclination. The sample consisted of 70 periodontally healthy adults, 35 with balanced faces and normal occlusions and 35 with Class III dentofacial deformities, with no history of previous orthodontic treatment. The buccolingual inclinations of all of the teeth and the maxillo-mandibular alveolar bone thickness were measured at three different heights (3, 6 and 8 mm) from the cementoenamel junction, using Dolphin® 3D software, from three-dimensional images generated by cone beam computed tomography. The error of the method was evaluated by means of intraclass correlations and Dahlberg\'s formula. Pearsons correlation test was used to verify the relationship between tooth inclination and bone thickness. The average thickness at 3 and 8 millimeters apical from cementoenamel junction, and the tooth inclinations were compared between the two groups using Student\'s t-test. The measures showed high reproducibility. The alveolar region corresponding to the upper cuspids appeared thinner, and the palatal area of the maxillary central incisors appeared thicker. In the mandible, the greatest measures of alveolar bone thickness were observed in the distobuccal region of the second molar. The data clearly showed lower values of the measurements evaluated at 3 mm from the cementoenamel junction for both groups. In individuals with normal occlusions, greater tooth inclinations were observed on the incisors, and these values decreased gradually toward the posterior region. In subjects with Class III dentofacial deformities, greater tooth inclinations were observed in the upper incisors and lower cuspids, and smaller tooth inclinations were observed on the buccal roots of the lower second molars. Regarding comparison between the groups, the second premolars, maxillary lateral and central incisors showed greater inclinations, and the second molars, first premolars and lower lateral and central incisors were less inclined in individuals with Class III deformities. All of the average values regarding alveolar bone thickness at 3 mm from cementoenamel junction were statistically lower in Class III subjects, compared to subjects with normal occlusions, and the majority of the evaluated values at 8 mm showed smaller values in individuals with Class III deformities. In addition, in individuals with Class III deformities, more positive statistically significant correlations were found between inclination and thickness in the lower teeth, whereas in subjects with normal occlusions, few statistically significant correlations were found between these two variables.

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