High-throughput mass spectrometry has discovered a plethora of candidates in the biomarker field, however, subsequent verification and validation studies are urgently needed to assess the potential of novel biomarkers in the detection of pancreatic cancer. We have conducted extensive verification and validation studies on two of our most promising biomarkers CUZD1 and LAMC2 with a total of 715 blood samples. In our study, both markers demonstrated consistent diagnostic ability of early- and CA19.9 negative-PDAC cases. When used in combination with CA19.9, CUZD1 and LAMC2 were shown to significantly improve the performance of CA19.9 alone in the diagnosis of PDAC patients. We speculate that CUZD1 and LAMC2 may be good candidates to be used in a panel for monitoring PDAC patients who do not express CA19.9 levels as well as for an aid in screening high risk populations. Further validation of these two proteins is warranted.

Patients with dementia are often unaware of their disease and do not seek medical attention; thus, health care providers must shift to "active detection" to identify at-risk patients early. No previous studies have focused on promoting this shift, so this study evaluates the efficacy of a new program to improve the knowledge and confidence of primary care providers in the early detection, diagnosis, and management of mild dementia. Physicians and nurses (n = 38) were recruited from 14 practices in Ontario, Canada. The Mild Dementia Knowledge Transfer Program was run at each practice. As a Neuroscience Master’s student I demonstrated the cognitive assessment procedures, and recipients assessed remaining patients with my guidance. Assessments included patient interviews using a Data Gathering Form –developed for the Program – to provide informal cognitive assessment, and the Montreal Cognitive Assessment (MoCA) test. The procedures were discussed between assessments to enhance learning. Later, recipients discussed the assessment results with the dementia specialist and myself; diagnoses and initial care plans were formulated collaboratively. Questionnaires measuring knowledge and confidence regarding detection, assessment and care of mild dementia were developed to measure change pre-post and three months after the Program. Linear mixed-effects models analysis with time as fixed effect and intercept as random effect was conducted to test change. Program recipients showed increases in knowledge-confidence score after the program (10.3; P < .001) paralleling increases in both knowledge and confidence sub-scores; there was no decline after three months (P = .83). No differences were observed between medical and nursing staff. The number of assessments done by recipients was positively associated with knowledge-confidence change (P = .01). Most recipients (70%) rated the program as excellent; 65% rated interactivity as the best part, 34% rated time commitment as the worst part, and 91% rated the program as making it easier to detect dementia. Due to the complex nature of dementia, the Program was performance-oriented, specialist-supported, clinic-based, and flexible to the needs of recipients. It showed acceptability and feasibility within primary care, and the results support its’ efficacy to improve primary care providers’ self-rated knowledge and confidence in mild dementia care. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2010-07-26 21:38:54.945

High-throughput mass spectrometry has discovered a plethora of candidates in the biomarker field, however, subsequent verification and validation studies are urgently needed to assess the potential of novel biomarkers in the detection of pancreatic cancer. We have conducted extensive verification and validation studies on two of our most promising biomarkers CUZD1 and LAMC2 with a total of 715 blood samples. In our study, both markers demonstrated consistent diagnostic ability of early- and CA19.9 negative-PDAC cases. When used in combination with CA19.9, CUZD1 and LAMC2 were shown to significantly improve the performance of CA19.9 alone in the diagnosis of PDAC patients. We speculate that CUZD1 and LAMC2 may be good candidates to be used in a panel for monitoring PDAC patients who do not express CA19.9 levels as well as for an aid in screening high risk populations. Further validation of these two proteins is warranted.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Magister Scientiae Dentium - MSc(Dent) (Community Oral Health) / The aim of this study was to establish whether there is any association between developing maxillary canine ectopia and various other dental anomalies using panoramic radiographs in the mixed dentition stage of development.

abstract: Breast cancer is the most common cancer and currently the second leading cause of death among women in the United States. Patients’ five-year relative survival rate decreases from 99% to 25% when breast cancer is diagnosed late. Immune checkpoint blockage has shown to be a promising therapy to improve patients’ outcome in many other cancers. However, due to the lack of early diagnosis, the treatment is normally given in the later stages. An early diagnosis system for breast cancer could potentially revolutionize current treatment strategies, improve patients’ outcomes and even eradicate the disease. The current breast cancer diagnostic methods cannot meet this demand. A simple, effective, noninvasive and inexpensive early diagnostic technology is needed. Immunosignature technology leverages the power of the immune system to find cancer early. Antibodies targeting tumor antigens in the blood are probed on a high-throughput random peptide array and generate a specific binding pattern called the immunosignature. In this dissertation, I propose a scenario for using immunosignature technology to detect breast cancer early and to implement an early treatment strategy by using the PD-L1 immune checkpoint inhibitor. I develop a methodology to describe the early diagnosis and treatment of breast cancer in a FVB/N neuN breast cancer mouse model. By comparing FVB/N neuN transgenic mice and age-matched wild type controls, I have found and validated specific immunosignatures at multiple time points before tumors are palpable. Immunosignatures change along with tumor development. Using a late-stage immunosignature to predict early samples, or vice versa, cannot achieve high prediction performance. By using the immunosignature of early breast cancer, I show that at the time of diagnosis, early treatment with the checkpoint blockade, anti-PD-L1, inhibits tumor growth in FVB/N neuN transgenic mouse model. The mRNA analysis of the PD-L1 level in mice mammary glands suggests that it is more effective to have treatment early. Novel discoveries are changing understanding of breast cancer and improving strategies in clinical treatment. Researchers and healthcare professionals are actively working in the early diagnosis and early treatment fields. This dissertation provides a step along the road for better diagnosis and treatment of breast cancer. / Dissertation/Thesis / Doctoral Dissertation Biological Design 2015

Os rins desempenham um papel fundamental no sistema urinário e sua principal função é a filtração do sangue. Uma das causas que podem comprometer o funcionamento dos rins é a Insuficiência Renal Aguda (IRA) que é definida como a diminuição da taxa de filtração glomerular (TFG) de forma rápida e inesperada, causando a perda da função renal. Essa doença apresenta um número significativo de internações e também óbitos. O marcador padrão usado nos exames laboratoriais é a creatinina sérica, no entanto, a concentração da creatinina sérica pode variar dependendo de vários fatores, como idade, sexo, nutrição, entre outros. Além disso, sua concentração não varia consideravelmente nas primeiras indicações da lesão renal. Dessa forma, o diagnóstico é tardio e a função renal já pode estar comprometida. A proteína cistatina C (CST3) vem sendo indicada como um novo marcador para a doença, mostrando superioridade especialmente para detectar pequenas variações da TFG. A concentração da cistatina C não varia significativamente com a idade, sexo e massa muscular. Assim, foi desenvolvido um imunossensor para detectar a cistatina C, usando a configuração de transistor de efeito de campo de porta estendida e separada (SEGFET). Os eletrodos foram caracterizados por várias técnicas como MEV, microscopia de força atômica, técnicas eletroquímicas e também foi analisada a sensibilidade do ouro. As etapas de construção do imunossensor, e a interação do anticorpo com concentrações crescentes da proteína foram verificadas através de técnicas eletroquímicas, na faixa de concentração de 3 a 100 ng.mL-1. Nas medidas no SEGFET observou-se uma mudança significativa da corrente após a adição da cistatina C e para as substâncias interferentes não. O imunossensor apresentou alta sensibilidade detectando concentrações bem baixas da proteína alvo. A curva analítica &#916;IDS% x [CST3] obteve-se L.D. = 0,75 ng.mL-1, L.Q. = 2,27 ng.mL-1 e r = 0,98122. A curva analítica &#916;VGS% x [CST3] obteve-se L.D. = 0,28 ng.mL-1, L.Q. = 0,87 ng.mL-1 e r = 0,99846. Embora tenha algumas limitações o imunossensor é inovador e apresenta muitas vantagens podendo ser aplicado futuramente para o diagnóstico da doença. / The kidneys play a key role in the urinary system and its main function is the filtration of blood. One of the causes that can compromise the functioning of the kidneys is the Acute Kidney Injury (AKI), which is defined as the quickly and unexpected decrease in Glomerular Filtration Rate (GFR), causing the loss of kidney function. This disease presents a significant number of hospitalizations and also deaths. The standard marker used in laboratory tests is serum creatinine, however, serum creatinine concentration may vary depending on a number of factors, such as age, sex, nutrition, and so on. In addition, its concentration does not vary considerably in the first indications of renal injury. Thus, the diagnosis is delayed and renal function may already be compromised. The cystatin C protein (CST3) has been indicated as a new marker for the disease, showing superiority especially for detecting small variations in GFR. The concentration of cystatin C does not vary significantly with age, sex and muscle mass. Thus, an immunosensor was developed to detect cystatin C using the extended and a separate gate field effect transistor (SEGFET) configuration. The electrodes were characterized by several techniques such as SEM, atomic force microscopy, electrochemical techniques and also the sensitivity of gold was analyzed. The construction of the immunosensor, and the interaction of the antibody with increasing concentrations of the protein were verified by electrochemical techniques, in the concentration range of 3 to 100 ng.mL-1. In the measurements in the SEGFET a significant change of the current was observed after the addition of cystatin C and for the interfering substances there was no difference. The immunosensor showed high sensitivity detecting very low concentrations of the target protein. The analytical curve &#916;IDS% x [CST3] was obtained L.D. = 0,75 ng.mL-1, L.Q. = 2,27 ng.mL-1 and r = 0,98122. The analytical curve &#916;VGS% x [CST3] was obtained L.D. = 0,28 ng.mL-1, L.Q. = 0,87 ng.mL-1 and r = 0,99846. Although it has some limitations the immunosensor is innovative and presents many advantages and can be applied in the future to diagnose the disease.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / The breast cancer has been established as a serious public health problem, not only by the growing number of cases diagnosed each year, but also by the financial investment that is required for diagnosis and treatment. The objective of this study was to evaluate actions for early detection and risk factors for breast cancer in women at a Basic Health Unit, Fortaleza, CearÃ. It was conducted a cross-sectional study, descriptive and analytical, with a quantitative approach, on shares of early detection and risk factors to the breast cancer. The research was developed in a Basic Unit of Family Health, Fortaleza, CearÃ, in the period from March to November of 2008. The population was based on the amount of annual gynecological attendances made by nurses, for a total of 1920. The sample was 320 women. It was used as technique for data collection a semi-structured interview and as instrument, the semi-structured form. For the analysis was used the chi-square test with the aid of SPSS version 15.0 in order to measure the association of variables, at 5% level of significance. The following results were obtained: the average age of interviewed women was 37, had family income below a minimum wage 139 (43.44%) of them; studied between 11 and 15 years of study, 192 (60%) of the total; reported first episode menstrual, aged over twelve years, 206 (64.38%); only 64 (20%) had entered the menopause and 238 (74.38%) had their first pregnancy, aged below 30 years of age; on breastfeeding, 210 (65.63%) breastfed their children; it was found that 177 (55.31%) make use contraceptive oral; had family history of breast cancer, 71 (22.19 %); affirm the habit of smoking 62 (19.38%); said drink alcohol 89 (27.81%). It was inferred that 252 (78.75%) know the BSE. The Clinical examination of the breasts is performed by 246 (76.87%) of respondents. It was observed that 46 (44.23%) reported perform mammography annually. It was detected that the years of study influenced on practice of BSE. However, there was a lack of association between the time of study and implementation of BCE and knowledge of mammography. As the range of income, this variable was associated only with the knowledge of the BSE and the mammography. It is noteworthy from the results of the research, that even with the technology developed in recent decades for the control of breast cancer, can not ignore the many factors that make the etiology of this neoplasm. Hence the need for greater effectiveness in detecting breast cancer, and early recognition of its risk factors / O cÃncer de mama tem se constituÃdo como um grave problema de saÃde pÃblica, nÃo sà pelo nÃmero de casos crescentes diagnosticados a cada ano, mas tambÃm pelo investimento financeiro que à necessÃrio para diagnÃstico e tratamento. Objetivou-se neste estudo, avaliar aÃÃes de detecÃÃo precoce e fatores de risco para cÃncer de mama, em mulheres atendidas em uma Unidade BÃsica de SaÃde, Fortaleza, CearÃ. Realizou-se um estudo transversal, descritivo e analÃtico com abordagem quantitativa, sobre aÃÃes de detecÃÃo precoce e fatores de risco para cÃncer de mama. A pesquisa foi desenvolvida em uma Unidade BÃsica de SaÃde da FamÃlia do municÃpio de Fortaleza-CearÃ, no perÃodo de marÃo a novembro de 2008. A populaÃÃo baseou-se na quantidade anual de atendimentos ginecolÃgicos realizados pelos enfermeiros perfazendo um total de 1920. A amostra obtida foi de 320 mulheres. Utilizou-se como tÃcnica de coleta de dados a entrevista semi-estruturada e como instrumento o formulÃrio semi-estruturado. Usou-se para a anÃlise, o teste qui-quadrado com o auxÃlio do SPSS versÃo 15.0, a fim de medir a associaÃÃo de variÃveis, ao nÃvel de 5% de significÃncia. Obtiveram-se os seguintes resultados: a idade mÃdia das mulheres entrevistadas foi de 37 anos; possuÃam renda familiar inferior a um salÃrio mÃnimo 139 (43,44%) delas; apresentaram escolaridade entre 11 e 15 anos de estudo, 192 (60%) do total; relataram primeiro episÃdio menstrual, com idade acima de doze anos, 206 (64,38%); apenas 64 (20%) haviam entrado na menopausa e 238 (74,38%) tiveram a primeira gestaÃÃo, na faixa etÃria abaixo de 30 anos de idade; quanto à amamentaÃÃo, 210 (65,63%) amamentaram seus filhos; constatou-se que 177 (55,31%) fazem uso anticoncepcional oral; tinham histÃrico familiar de cÃncer de mama, 71 (22,19%); declararam o hÃbito de fumar 62 (19,38%); afirmaram ingerir bebida alcoÃlica 89 (27,81%). PÃde-se inferir que 252 (78,75%) conhecem o AEM. O exame clÃnico das mamas à realizado em 246 (76,87%) das entrevistadas. Pode-se observar ainda que 46 (44,23%) relataram realizar o exame mamogrÃfico anualmente. Constatou-se que o tempo de estudo influencia na prÃtica do AEM. PorÃm, verificou-se a nÃo existÃncia de associaÃÃo entre o tempo de estudo e a realizaÃÃo do ECM e o conhecimento da mamografia. Quanto à faixa de renda, houve associaÃÃo desta variÃvel somente com o conhecimento do AEM e com o da mamografia. Vale ressaltar, a partir dos resultados da pesquisa, que mesmo com a tecnologia desenvolvida nas Ãltimas dÃcadas para o controle do cÃncer de mama, nÃo se podem desconsiderar os mÃltiplos fatores que compÃem a etiologia desta neoplasia. DaÃ, a necessidade de uma maior efetividade na detecÃÃo do cÃncer de mama e reconhecimento precoce dos seus fatores de risco

Introdução: Ainda que curável, a Tuberculose (TB) permanece no cenário epidemiológico mundial e nacional e parece estar distante de ser eliminada, uma vez que sua relação com as iniquidades sociais é inegável. Estima-se que, em 2015, 3 milhões de pessoas não tiveram a doença diagnosticada. O diagnóstico precoce é fundamental como uma estratégia preventiva para se evitar mortes e sofrimento, rompendo a cadeia de transmissão. No Município de São Bernardo do Campo-SP, a busca ativa de sintomáticos respiratórios tem se apresentado abaixo das metas estimadas. Objetivo: Elaborar um plano de intervenção para o aprimoramento da busca ativa de sintomáticos respiratórios no âmbito da Atenção Primária. Método: Trata-se de pesquisa-ação, realizada com 14 profissionais de saúde: coordenadores de unidade básica de saúde, médicos, enfermeiros, técnicos de enfermagem e agentes comunitários, representando um Território de Saúde do Município. À luz das diretrizes da Política Nacional da Atenção Básica e do Programa Nacional de Controle da Tuberculose, por meio de grupo focal, com sessões realizadas em 2016, a detecção precoce e a busca ativa de sintomáticos respiratórios foram problematizadas, tendo sido elaborado um plano de intervenção para reverter a situação de baixa busca ativa nas unidades básicas de saúde. Resultados: Os depoimentos dos participantes revelam que a TB ainda carreia estigma e preconceito, que dificultam a busca ativa de casos. Verificou-se que a busca ativa é expressivamente atribuída ao agente comunitário e não envolve outros membros da equipe; também se verificou a não utilização de espaços estratégicos na unidade de saúde para estimular a interação com a população e informá-la a respeito do agravo. Outro aspecto que emergiu refere-se ao diagnóstico da doença, realizado em unidades de pronto atendimento e de urgência e não no âmbito da atenção primária. Ademais, os profissionais de saúde reivindicam capacitação para a abordagem da TB, incluindo a incorporação de tecnologias leves na busca ativa. Elaborou-se um plano de intervenção com ações intra e extra-muros, além de indicar-se a necessidade de monitoramento dos indicadores epidemiológicos no âmbito institucional. Tratando-se de pesquisa-ação, algumas ações relacionadas à busca ativa de casos já tiveram início, envolvendo todas as unidades básicas de saúde. Conclusão: O plano de intervenção construído contribuirá para o controle da TB na região. Ainda assim, entende-se que o controle da doença requer intervenções amplas e que envolvem a qualificação dos profissionais de saúde, a participação da população e, sobretudo, políticas intersetoriais que modifiquem as condições sociais e de vulnerabilidade. / Introduction: Although curable, Tuberculosis (TB) remains in the worldwide and national epidemiological scenery and seems to be far from being eliminated, since its relationship with social inequalities is undeniable. It is estimated that in 2015, 3 million people did not have the disease diagnosed. The early diagnosis is essential as a preventive strategy to prevent deaths and suffering, breaking the transmission chain. In São Bernardo do Campo SP, the active search for respiratory symptoms has been shown below the estimated targets. Objective: To elaborate a plan of action to improve the active search for respiratory symptoms within the Primary Attention. Method: It is an action-research, performed with 14 health professionals: coordinators of basic health units, doctors, nurses, nursing technicians and community workers, representing a City Health Territory. In the light of the guidelines of the National Policy of Primary Attention and the National Program for Tuberculosis Control, through focus group, with sessions held in June of 2016, the question related to the early detection and active search for respiratory symptoms was questioned, having the plan of action been drawn up to reverse the situation in the basic health units. Results: The statements of the participants reveal that TB still carries stigma and prejudice, which hinder the active search for cases. It was found that the active search is significantly attributed to the community worker and does not involve other team members; there was also no use of the strategic spaces in the health unit to encourage interaction with the population and inform them about the grievance. Another aspect that has emerged concerns the diagnosis of the disease, conducted in emergency care and emergency units and not as part of the primary attention. In addition, health professionals claim training for TB approach, including the active search, mainly as regards the use of lightweight technologies. It was developed an intervention plan with intra and extramural actions, besides to indicate the need for monitoring epidemiological indicators at the institutional level. As an action-research, some actions related to the active search for cases already started, involving all basic health units. Conclusion: The intervention plan will contribute to the control of TB in the region, and it is understood that the control of the disease requires broad interventions, which involve the training of health professionals, public participation and, especially, intersectoral policies to modify social and vulnerability conditions.

>Magister Scientiae - MSc / Type 2 diabetes mellitus (T2DM), a metabolic disease characterized by chronic hyperglycemia, is the most prevalent form of diabetes globally, affecting approximately 95 % of the total number of people with diabetes i.e. approximately 366 million. Furthermore, it is also the most prevalent form in South Africa (SA), affecting approximately 3.5 million individuals. This disease and its adverse complications can be delayed or prevented if detected early. Standardized diagnostic tests for T2DM have a few limitations which include the inability to predict the future risk of normal glucose tolerance individuals developing T2DM, they are dependent on blood glucose concentration, its invasiveness, and they cannot specify between T1DM and T2DM. Therefore, there is a need for biomarkers which could be used as a tool for the early and specific detection of T2DM. MicroRNAs are small non-coding RNA molecules which play a key role in controlling gene expression and certain biological processes. Studies show that dysregulation of microRNAs may lead to various diseases including T2DM, and thus, may be useful biomarkers for disease detection. Therefore, identifying biomarkers like microRNAs as a tool for the early and specific detection of T2DM, have great potential for diagnostic purposes. The main focus of this investigation, therefore, is the early detection of T2DM by the identification and validation of novel biomarkers. Furthermore, based on previous studies, the aim of the investigation was to identify differentially expressed miRNAs as well as identify their potential target genes associated with the onset and progression of T2DM. An in silico approach was used to identify miRNAs found to be differentially expressed in the serum/plasma of T2DM individuals. Three publically available target prediction software were used for target gene prediction of the identified miRNA. The target genes were subjected to functional analysis using a web-based software, namely DAVID. Functions which were clustered with an enrichment score > 1.3 were considered significant. The ranked target genes mostly had gene ontologies linked with “transcription regulation”, “neuron signalling, and “metal ion binding”. The ranked target genes were then split into two lists – an up-regulated (ur) miRNA targeted gene list and a down-regulated (dr) miRNA targeted gene list. The in silico method used in this investigation produced a final total of 4 miRNAs: miR-dr-1, miR-ur-1, miR-ur-2, and miR-ur-3. Based on the bioinformatics results, miR-dr-1 and its target genes LDLR, PPARA and CAMTA1, seemed the most promising miRNA for biomarker validation, due to the function of the target genes being associated with T2DM onset and progression. The expression levels of the miRNAs were then profiled in kidney tissue of male Wistar rats that were on a high fat diet (HFD), streptozotocin (STZ)-induced T1DM, and non-diabetic control rats via qRT-PCR analysis. The hypothesis was that similar miRNA expression would be found in the HFD kidney samples compared to serum expression levels of the miRNA obtained from the two databases, since kidneys are involved in cleansing the blood from impurities. This hypothesis proved to be true for all miRNAs except for miR-ur-2. Additionally, miR-ur-1 seemed the most significant miRNA due to it having different expression ratios for T1DM and T2DM (i.e. -7.65 and 4.2 fold, respectively). Future work, therefore, include validation of the predicted target genes to the miRNAs of interest i.e. miR-dr-1: PPARA and LDLR and miR-ur-1: CACNB2, using molecular approaches such as the luciferase assays and western blots.