Дисертації з теми "Medicina quantitativa"

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A cartilagem articular à um tecido avascular constituÃdo por condrÃcitos dispersos em uma matriz extracelular abundante (MEC) que reveste as superfÃcies articulares e protege as extremidades Ãsseas. AlÃm do fluido intersticial, a MEC à composta por proteoglicanos, glicosaminoglicanos (GAGs) e glicoproteÃnas. DoenÃas articulares, como a osteoartrite (OA), promovem a degradaÃÃo da cartilagem articular e esclerose do osso subcondral, levando à dor crÃnica e comprometimento funcional das articulaÃÃes. Neste contexto, a quantificaÃÃo de GAGs à utilizada para estudar o papel das alteraÃÃes fisiolÃgicas ou patolÃgicas da cartilagem articular. Assim, o objetivo do trabalho foi avaliar as alteraÃÃes bioquÃmicas da cartilagem articular humana e de rato com ou sem a OA. As cartilagens humanas foram obtidas de pacientes submetidos à artroplastia por OA ou por fratura. Ratos Wistar machos (150-180g) foram submetidos à osteoartrite experimental que consiste na transecÃÃo do ligamento cruzado anterior (TLCA). Grupo sham foi submetido apenas ao procedimento cirÃrgico, sem transecÃÃo. Inicialmente, as amostras de cartilagem foram submetidas à aÃÃo do complex enzimÃtico PROLAV 750R, obtendo-se ao final do processo, os GAGs. Esses foram identificados e quantificados em gel de agarose (0,6%) e a massa molar foi avaliada em gel de poliacrilamida (6% w/v). Os resultados foram expressos como mÃdia  erro padrÃo da mÃdia (e.p.m.), submetidos à ANOVA e teste de Tukey (P<0,05) ou teste âtâ de Student (P<0,05). Em ratos, o rendimento da degradaÃÃo da cartilagem pela PROLAV 750R foi significativamente diminuÃda apÃs 70 dias de TLCA (P<0,05). Quanto à quantificaÃÃo de GAGs, houve um aumento significativo do conteÃdo de GAGs apÃs 70 dias de TLCA. Em humanos, o percentual de massa degradada pela PROLAV foi reduzida na presenÃa de OA. Os pacientes com OA com idade inferior a 80 anos apresentaram aumento significativo da quantidade de GAGs, quando comparado ao grupo controle. Quanto à mobilidade eletroforÃtica, GAGs de pacientes com OA apresentaram alteraÃÃo da massa molar. Esses achados mostram que tanto a cartilagem proveniente de pacientes acometidos por OA quanto animais submetidos à OA experimental apresentam menor rendimento à degradaÃÃo enzimÃtica, aumento da quantidade de CS e alteraÃÃo da massa molar.
Articular cartilage is na avascular tissue composed of chondrocytes scattered in an abundant extracellular matrix (ECM) that lines the joint surfaces and protects the bone ends. In addition to the intersticial fluid, the ECM is composed of proteoglycans, glycosaminoglycans (GAGs) and glycoproteins. Joint diseases such as osteoarthritis (OA), promote the degradation of articular cartilage and subchondral bone sclerosis, leading to chronic pain and functional impairment of the joints. In this context, the quantification of GAGs is used as a means to study the physiological or pathological changes of articular cartilage. The objective this study was to evaluate the biochemical changes of the articular cartilage of human and rat normal or affected by OA. The human cartilage were obtained from patients submitted to arthroplasty for OA or fracture. Male Wistar rats (150-180g) were submitted to the anterior cruciate ligament transection (ACLT). Sham group was submitted to only to surgery without transection. Initialy, the cartilage samples were submitted to the action of the enzymatic complex PROLAV 750R, getting to the end of the process, the GAGs. These were identified and quantified in agarose gel (0.6%) and molar mass was assessed in polyacrylamide gel (6% w/v). The results were expressed as mean  standard error of mean (S.E.M.) were submitted to ANOVA and Tukeyâs test (P<0.05) or âtâ test of Student (P<0.05).In rats, the effective proteolysis was significantly decreased after 70 days of ACLT (P<0.05). In the quantification of GAGs, there was a significant increase in GAG content after 70 days of ACLT. In humans, the percentage of mass degraded by PROLAV was altered by presence of OA. The OA patients under 80 years of age showed a significant increase in the amount of GAGs compared to the control group. In the electrophoretic mobility, GAGs of patients with OA showed abnormalities of the molar mass. These findings show that both cartilage from patients affected by OA as experimental animals subjected to OA have lower effective proteolysis, increasing the amount of CS and alteration of the molar mass.

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Muitos são os materiais utilizados atualmente para regeneração óssea na área da medicina dentária e, dentre os materiais mais utilizados, é possível citar os materiais de origem xenógena e os materiais aloplásticos. Os defeitos ósseos congênitos ou adquiridos, seja por problemas periodontais, perda óssea em consequência de edentulismo parcial ou total, traumatismos, necessidade de elevação do seio maxilar e outras situações onde as bases ósseas são finas ou estreitas para a colocação de implantes, têm promovido constantes estudos nessa área e a necessidade crescente em melhorar o processo de regeneração óssea e osteointegração tem elevado os esforços na busca por materiais sintéticos cada vez mais biocompatíveis, de fácil manuseio, moldáveis e, principalmente com propriedades cada vez mais osteogênicas. Esse trabalho tem como objetivo a revisão sistemática da literatura, publicada nos últimos 10 (dez) anos, com foco nos estudos comparativos entre os diferentes materiais aloplásticos e xenógenos existentes para a regeneração óssea. As publicações selecionadas utilizaram materiais aloplásticos e xenógenos no mesmo estudo e incluiram análise histomorfométrica, com a percentagem de volume ósseo formado, para a compararação dos resultados. A hipótese que esse trabalho propôs responder é se há diferenças significativas entre os materiais xenógenos e os sintéticos, quando se aplica como principal requisito o volume de novo osso formado com esses materiais, sendo que H0 é que não há diferenças estatísticas significativas entre os materiais de regeneração óssea analisados. A variety of materials for bone regeneration are used in modern dental and maxillofacial surgeries. Among the materials most used are xenograft and synthetic materials. Congenital or acquired bone defects, such as periodontal diseases, bone loss from partial or total edentulism, trauma, the necessity of sinus augmentation or other situations where the bone is too thin to have implants loaded have lead the researchers to pursue their investigations into the development of new synthetic materials that enhance the process of bone regeneration and osteointegration. These materials also increase biocompatibility, ease of handling and moldability and improve the osteogenesis process. The objective of this paper is to do a systematic review and a meta-analysis between different types of xenogenous and synthetic graft materials investigated through comparative studies published in the last 10 years. All the included publications had to be comparative studies with at least one synthetic cement material and one xenograft material, excluding membranes. To be included in this meta-analysis, the comparative studies had to include histomorphometry and had to measure the percentage of bone formation. For this study, it is hypothesized for H0 that there is no significant statistical differences between xenograft bone material and synthetic bone materials regarding the percentage volume of new bone growth.

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In this thesis, made up of two experiments, in different processes of testicular degeneration in rams it was evaluated the efficiency of ultrasonography with the grayscale histogram technique. The First Experiment was carried out with the aim of monitoring the progression of induced ischemic degeneration validate analyzes of echogenicity and ecotexture patterns, also evaluating the scrotal perimeter and testicular volume. The males (n = 6), aged 11 and 18 months, underwent testicular biometry analysis to obtain the scrotal and testicular volume, and acquisition of ultrasound images were performed to determine echogenicity and echotexture values in the GIMP software 2.8® for determination of pre-ischemia patterns. The measurements of these parameters were performed before mechanical ischemia induced with burdizzo (D0) and on days 1 (D1), 4 (D4), 8 (D8), 16 (D16), 24 (D24), 35 (D35) and 50 (D50). The value of echogenicity in the healthy testicle was 105.01 ± 8.23 and that of the ecotexture by echo variation was 13.24 ± 0.88. The behavior of the echogenicity, represented by the numerical value of the pixel, showed that the mechanical impedance of the testicular irrigation exerted influence (P <0.05) already from the first day (D1) after this procedure, which continued in decline that was observed in D4 with a value of 50.11 ± 7.21 (P <0.05). It was remained the pixel value constant until the 35th day and was only recovered at the end of the experiment (D50), when the fibrosis process replaced. The tissues of the testicular parenchyma and provided a significant increase (P <0.05) in echogenicity to a value of 62.19 ± 7.15, similar to the value verified in D1 (P> 0.05). The behavior of the numerical value of the ecotexture, which was initially 13.24 ± 0.88, showed that only from the D4, there was an increase (P <0.05) in the homogeneity of the testicular parenchyma ecotexture relative to the D0 decreasing to values Of 11.01 ± 1.61. A fact also observed on the other days of evaluation, except for the one performed in the D50 that increased the heterogeinity to 14.42 ± 1.77. It is ended that for an acute lesion, echocardiographic values obtained by amplitude of echo variation is not sufficient to support a precise diagnostic evaluation, being necessary to correlate with the alteration of echogenicity values and that, macroscopically; testicular degeneration is characterized by the reduction of the scrotal perimeter and testicular volume. The Second Experiment aimed to evaluate the role of quantitative gray scale analysis in the ultrasonographic images of sheep testicles with scrotal insulation, accompanying their degeneration and recovery phases. We used six adult non - defined animals aged 18 to 20 months. We divided the experiment into three periods. It performed in the pre-insulation period, semen analysis, testicular biometry and ultrasonographic imaging for subsequent quantitative computational analysis of ecotexture and echogenicity using the gray histogram to establish a normality pattern. It placed in the scrotal insulation phase, tissue pouches, involving the scrotum, with a double wall and inner layer of hydrophobic cotton with about five mm. (D4I). We performed measurements of testicular biometric, spermogram, and ultrasonographic imaging. The post-insulation phase started with the withdrawal of the bags, it considered this day as day 0 and testicular measurements, semen collections, and testicular measurements and ultrasound monitoring were performed every seven days until the seminal parameters were recovered. In testicular biometry, the length and scrotal volume measurements decreased on the first day of the post-insulation period (P <0.05). Among the sperm parameters, a decrease (P <0.05) was observed, with 4 days of thermal stress of motility, vigor and turbulence, 35 ± 20.74%, 1.83 ± 0.75 (0-5), 2, 3 ± 0.47 (0-5) respectively, associated with a decrease in echogenicity, which was initially 100 ± 4.9 and 99.69 ± 5.3 pixel intensity. After four days of thermal stress, echogenicity had a Drop to values of 73.1 ± 14.2 (P <0.05) increase for values close to those of the pre-insulation period that occurred at 63 days post-insulation period. The ecotexture did not change in the values initially (P> 0.05) without variation in the ecotexture. Ecogenicity showed a precocity with respect to the other parameters in return to the standards defined in the preinsulation period. It was concluded that the induction of thermal stress was characterized by a reduction of testicular biometry, a decline in seminal quality and a decrease in pixel intensity in the ultrasound image, the latter being a sensitive parameter both in the acute phase together with motility, vigor and turbulence, and Testicular recovery, showing itself earlier than other parameters.
Nesta Tese, constituída de dois experimentos, avaliou-se a eficiência da ultrassonografia com a técnica de histograma da escala de cinza em diferentes processos de degeneração testicular em ovinos. O Primeiro Experimento foi conduzido objetivando-se acompanhar a progressão da degeneração isquêmica testicular induzida com intuito de validar as análises de padrões de ecogenicidade e ecotextura, avaliando-se também o perímetro escrotal e o volume testicular. Os machos (n=6), com idade 11 e 18 meses foram submetidos a análise de biometria testicular com obtenção do perímetro escrotal e volume testicular, e aquisição de imagens ultrassonográficas foram realizadas para determinação de valores de ecogenicidade e ecotextura no software GIMP 2.8® para determinação de padrões pré isquemia. As aferições desses parâmetros foram realizadas antes da isquemia mecânica induzida com burdizzo (D0) e nos dias 1 (D1), 4 (D4), 8 (D8), 16 (D16), 24 (D24), 35 (D35) e 50 (D50). O valor da ecogenicidade no testículo hígido foi de 105,01 ± 8,23 e o da ecotextura pela variação do eco foi de 13,24 ± 0,88. O comportamento da ecogenicidade, representado pelo valor numérico de pixel, mostrou que o impedimento mecânico da irrigação testicular exerceu influência (P < 0,05) já a partir do primeiro dia (D1) após o procedimento, o qual continuou em declínio que foi observado no D4 com valor de 50,11±7,21 (P < 0,05) O valor numérico de pixel manteve-se constante até o 35o dia, sendo apenas recuperado ao final do experimento (D50), quando o processo de fibrose substituiu os tecidos do parênquima testicular e proporcionou significativo aumento (P < 0,05) da ecogenicidade para valor de 62,19±7,15, semelhante ao valor verificado em D1 (P>0,05). O comportamento do valor numérico da ecotextura que inicialmente foi 13,24±0,88, mostrou que somente a partir do D4 ocorreu aumento (P < 0,05) da homogeneidade do parênquima testicular em relação ao D0 diminuindo para valores de 11,01±1,61, fato também verificado nos demais dias de avaliação, exceto aquela realizada no D50 que aumentou a heterogeneidade subindo para 14,42±1,77. Conclui-se que perante uma lesão aguda, os valores da ecotextura obtidos pela amplitude de variação do eco não são suficientes para respaldar uma avaliação diagnóstica precisa, sendo necessário correlacionar à alteração dos valores da ecogenicidade e que macroscopicamente, a degeneração testicular se caracteriza pela redução significativa do perímetro escrotal e do volume testicular. O Segundo Experimento objetivou-se avaliar o papel da análise quantitativa da escala de cinza nas imagens ultrassonográficas de testículos de ovinos com insulação escrotal, acompanhando sua fase de degeneração e recuperação. Foram utilizados 6 animais adultos sem raça definida com idade entre 18 - 20 meses de idade. O experimento foi dividido em três períodos. No período pré-insulação, foram realizados exames de análise do sêmen, biometria testicular e aquisição de imagens ultrassonográficas para posterior análise computacional quantitativa da ecotextura e da ecogenicidade através do histograma de cinza e assim estabelecer um padrão de normalidade. Na fase de insulação escrotal, colocou-se bolsas de tecido, envolvendo o escroto, com dupla parede e camada interna de algodão hidrófobo com cerca de 5 mm de espessura tendo a duração de oito dias, ao quarto dia (D4I) realizou-se medidas da biometria testicular, espermograma e análises da imagens ultrassonográficas. A fase de pós-insulação iniciou com a retirada das bolsas sendo considerado este dia como o dia 0 e foram realizadas aferições testiculares, coletas de sêmen, aferição das medidas testiculares e acompanhamento ultrassonográfico a cada sete dias, até a recuperação dos parâmetros seminais. Na biometria testicular observou diminuição das medidas de comprimento e volume escrotal no primeiro dia do período pós-insulação (P < 0,05). Dentre os parâmetros espermáticos foram observados diminuição (P < 0,05), com 4 dias de estresse térmico da motilidade, vigor e turbilhonamento, 35±20,74 %, 1,83 ±0,75 (0-5), 2,3±0,47 (0-5) respectivamente, associado a uma diminuição da ecogenicidade, que incialmente era 100±4,9 e 99,69±5,3 de intensidade pixel. Após quatro dias de estresse térmico, a ecogenicidade teve uma queda para valores de 73,1±14,2 (P < 0,05) aumento para os valores próximos aos do período pré-insulação que ocorreu aos 63 dias do período pós-insulação. A ecotextura não apresentou variação nos valores inicialmente (P>0,05). Ecogenicidade demonstrou uma precocidade com relação aos outros parâmetros no retorno aos padrões definidos no período pré-insulação. Conclui-se portanto que a indução do estresse térmico caracterizou com redução da biometria testicular, declínio na qualidade seminal e diminuição da intensidade pixel na imagem ultrassonográfica, esta última sendo um parâmetro sensível tanto na fase aguda em conjunto a com motilidade, vigor e turbilhonamento quanto na recuperação testicular, mostrando-se mais precocemente que outros parâmetros.

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Neurofibromatosis (NF) is a neuroectodermal abnormality composed of a set of conditions having clinical manifestations which mainly affect the skin, eyes, bones, nervous system and eventually have repercussions on other internal organs. Its inheritance pattern is normally autosomally dominant and it has been considered one of the most frequent genetic diseases in the human race with a high penetration and variable expressiveness. This work studies the genetical-clinical aspects, makes a quantitative evaluation of the mastocytes and the extracellular matrix in neurofibromas in a group of thirty patients diagnosed with NF-1 and makes a comparison with a control group of ten normal individuals. The genetical-clinical evaluation confirmed the diagnosis of type 1 NF (NF-1) in all the patients. The main characteristics were neurofibromas, caféau-lait spots (CLS), Lisch nodules and axial or inguinal freckles. The multiple neurofibromas and Lisch nodules were considered to be exclusive to NF-1. Macrocephaly, in isolation, was not sufficient for the diagnosis of NF-1 and the other characteristics observed were considered complications. With the tissue from biopsies of both normal skin and neurofibromas of these patients, ten histologic sections were obtained. These were stained using hematoxylin-eosine, Gömöri trichrome, pricrosirius-hematoxylin, silver and iron-hematoxylin impregnation to evaluate the components of the extracellular matrix and staining using Toluidine blue to count the mastocytes. There was a significant increase in the number of mastocytes and the extracellular matrix was altered compared to the normal skin. This alteration was seen by the high cellularity associated with an increased density of fibrous components, specifically collagen type III, the scarcity or almost nonexistence of amorphous fundamental substance and the lack of elastic tissue. These findings seem to have an important role in the formation of neurofibromas and can help in the treatment of NF.
A Neurofibromatose (NF), é uma anormalidade neuroectodérmica constituída por um conjunto de condições com manifestações clínicas que comprometem principalmente a pele, olhos, ossos, sistema nervoso e, eventualmente, com repercussões aos outros órgãos internos. Seu padrão de herança é autossômica dominante e tem sido considerada uma das mais freqüente na espécie humana com penetrância elevada e expressividade variável. No presente trabalho, estudou-se os aspectos genético-clínicos, realizou-se a avaliação quantitativa dos mastócitos e da matriz extracelular em neurofibromas de um grupo de 30 pacientes diagnosticados como NF-1 e comparou-se com o grupo controle constituído de 10 indivíduos normais. A avaliação genético-clínica confirmou o diagnóstico de NF-1 em todos os pacientes. As características principais ou major foram os neurofibromas, MCCL, nódulo de Lisch e sardas axilares ou inguinais. Os neurofibromas múltiplos e os nódulos de Lisch foram considerados exclusivos de NF-1. A macrocefalia, quando isoladamente, não demonstrou ser suficiente para o diagnóstico de NF1 e as outras características foram consideradas como complicações. Em material obtido de biópsias de pele normal e de neurofibromas desses pacientes, realizou-se 10 cortes histológicos os quais foram submetidos às técnicas de coloração pela hematoxilina-eosina, tricrômio de gomori, tricrômio do pricrosirius-hematoxilina, impregnação pela prata e hematoxilinaférrica para a avaliação dos componentes da matriz extracelular e pela coloração com o azul de toluidina para a contagem de mastócitos. Houve diferença significativa no número dos mastócitos que encontraram-se aumentados e, quanto a matriz extracelular, apresentou-se alterada em comparação com a pele normal pela alta celularidade associada à elevada densidade dos componentes fibrosos, particularmente do colágeno tipo III, com escassez ou quase ausência de substância fundamental amorfa e ausência de material elástico. Tais achados parecem ter um papel significativo na formação dos neurofibromas e podem colaborar na terapêutica da NF.

Obiettivo di questa tesi di dottorato è di mostrare un metodo sperimentale e innovativo attraverso il quale è possibile realizzare una calzatura personalizzata e sensorizzata mediante un processo di fabbricazione additiva di Fused Deposition Modelling (FDM). I recenti progressi tecnologici e lo sviluppo di nuovi approcci nella realizzazione di dispositivi su misura, come la prototipazione rapida a mezzo di scansione laser e la stampa additiva, hanno evidenziato la potenzialità di un miglioramento significativo della produzione di questi dispositivi in termini di riproducibilità, qualità del prodotto e abbattimento dei costi. La riproducibilità del processo e la validazione del dispositivo si sono basate sull’interazione di diverse competenze: cliniche, biomeccaniche, di scienza dei materiali e di design. In seguito ad uno studio sulle proprietà meccaniche dei materiali esistenti e al perfezionamento del processo di design della protesi personalizzata è stato ideato un sistema per creare all’interno delle ortesi uno spazio dedicato alla sensoristica. Queste protesi dotate di dispositivi tecnologici come i sensori inerziali, gravimetrici, GPS e sistemi di trasmissione wireless potranno essere utili non solo per migliorare l’assetto del piede, organo sensoriale e motorio di centrale importanza per il sistema biomeccanico e posturale-propriocettivo del corpo umano, ma anche come strumento di diagnosi quantitativa e qualitativa nonché come sistema di monitoraggio dei risultati clinici in ambito neurologico, ortopedico e riabilitativo.
The aim of this doctoral thesis is to demonstrate an innovative method that achieves a customized and sensorized shoe using an additive manufacturing process of Fused Deposition Modelling (FDM). The recent technological advances and the development of new approaches in the creation of custom-made devices, such as rapid prototyping by means of laser scanning and additive printing, have highlighted the potential for a significant improvement in the production of these devices in terms of reproducibility, quality of the product and cost reduction. The reproducibility of the process and the validation of the device were based on the interaction of different competencies: clinical, biomechanical, material and design science. Following a study on the mechanical properties of existing materials and the improvement of the process for designing the customized prosthesis, a system was devised to create a space dedicated to sensors inside the orthoses. These prostheses, fitted with technological devices such as inertial, gravimetric, GPS and wireless transmission sensors, will be useful not only for improving the position of the foot (a sensory and motor organ of central importance for the biomechanical and postural-proprioceptive system of the human body) but will lead also as a quantitative and qualitative diagnostic tool, as well as a system for monitoring clinical results in the neurological, orthopaedic and rehabilitation fields.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Quantitative computerized tomography (QCT) is a highly sensitive technique, applied accurately diagnose loss of bone mass, bone mineral densitometry call with great advantages over plain radiography, but the lack of it limiting values for its clinical application. This study had the following objectives: establishing mean values of radiodensity the vertebral body of the second lumbar vertebra through the TCQ in cats, aspects involved in the pathophysiology of osteopenia induced by castration; study effects of depletion of estrogens radiodensity evaluate the characteristics of the female feline species of each experimental group, between the entire young cats and castrated adult cats spayed and not more than 6 years in a total of 22 animals. Comparing the degree of normality for young adult cats, and related. Statistically diseases was proven to be a reduction of bone mass in castrated cats over 6 years second lumbar vertebra L2.
A tomografia computadorizada quantitativa (TCQ) é uma técnica de alta sensibilidade, aplicada com precisão no diagnóstico de perda de massa óssea, chamada de densitometria mineral óssea, com grandes vantagens em relação à radiografia simples, porém a falta de valores de normalidade é limitante para a sua aplicação clínica. O presente trabalho teve os seguintes objetivos: estabelecer valores médios da radiodensidade do corpo vertebral da segunda vértebra lombar, através da TCQ, em gatas, aspectos envolvidos na fisiopatologia da osteopenia induzida pela castração; estudar efeitos da depleção dos estrógenos e avaliar as características da radiodensidade das fêmeas da espécie felina de cada grupo experimental, entre as gatas jovens inteiras e as gatas adultas castradas e não castradas acima de 6 anos, em um total de 22 animais. Comparando o grau de normalidade para as gatas adultas jovens e as patologias relacionadas. Estatisticamente comprovou-se uma redução de massa óssea em gatas castrada com mais de 6 anos na segunda vértebra lombar L2.

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Apesar das evidencias de níveis de exposição ao mercúrio capazes de produzirem danos neurológicos às comunidades ribeirinhas da bacia do rio Tapajós, poucos estudos clínicos avaliaram alterações de funções neurológicas, principalmente as somatossensoriais, consideradas como as manifestações iniciais da intoxicação por metilmercúrio. Neste estudo avaliaram-se os níveis atuais de exposição ao mercúrio e as manifestações somatossensoriais em ribeirinhos adultos residentes em comunidades situadas em diferentes regiões hidrográficas. Duas, na bacia do Tapajós e uma na bacia do Tocantins. Participaram do estudo 78 ribeirinhos em Barreiras, 30 em São Luís do Tapajós (bacia do Tapajós) e 49 no Furo do Maracujá (Tocantins), com idade entre 13 e 53 anos, de ambos os sexos. Concentrações de mercúrio total foram quantificadas em cabelo através da espectrofotometria de absorção atômica e a avaliação neurológica foi realizada por exame convencional e através de medidas quantitativas para sensibilidade tátil por monofilamentos de Semmes-Weinstein, sensibilidade vibratória e discriminação de dois pontos. As concentrações de mercúrio nas comunidades da bacia do Tapajós foram maiores que a do Tocantins (p<0,0001). A avaliação das alterações neurológicas não mostrou diferença significativa entre as comunidades das áreas exposta e controle para as alterações observadas através do exame neurológico convencional, exceto para desvio da marcha (p <0,05). Os limiares do tato por monofilamentos de Semmes-Weinstein, exceto para o peito esquerdo; vibração, exceto para o esterno superior, e da discriminação de dois pontos foram maiores nos indivíduos em área de exposição quando comparados com os da área controle (p<0,05). Na correlação dos limiares com as concentrações atuais do Hgtotal no cabelo, correspondência diretamente proporcional só foi observada para os limiares do tato por monofilamentos de Semmes-Weinstein do lábio inferior (p-valor<0,0001). Conclui-se que alterações somatossensoriais leves predominaram nas áreas de exposição ao metilmercúrio. Manutenção do monitoramento da exposição, orientação em relação às medidas de saúde pública e novos estudos clínicos utilizando testes somatossensoriais quantitativos são necessários para esclarecimento da ocorrência de casos clínicos de intoxicação nas áreas ribeirinhas contaminadas por mercúrio.
Despite evidence that exposure levels to mercury can produce neurological damage to the coastal communities of the Tapajos River basin, only a few clinical studies have assessed changes of neurological functions, especially somatosensory disturbance, considered as the initial manifestations of methylmercury poisoning. In this study we evaluated the current levels of exposure to mercury and sensory symptoms in adults from Riverside communities located in different river basins. Two in the Tapajós River basin and one in Tocantins basin. Participating in this study were 78 residents in Barreiras, 30 in São Luís do Tapajós (Tapajós River basin) and 49 in Furo do Maracujá (Tocantins basin), aged between 13 and 53 years, of both sexes. Total hair mercury concentrations were quantified by atomic absorption spectrophotometry and the neurological evaluation was carried out by conventional examination and by quantitative measures for tactile sensation by Semmes-Weinstein monofilaments, vibration sensation and two points discrimination. Concentrations of mercury in the Tapajós River basin communities were higher than that of Tocantins (p<0.0001). The evaluation of neurological changes showed no significant difference between the communities of exposed areas and control for the changes observed by conventional neurological examination, except for gait deviation (p<0.05). Thresholds for tactile sensation by Semmes-Weinstein monofilaments (except for the left chest), vibration sensation (except for the upper sternum) and discrimination of two points were higher in the subjects in the area of exposure when compared with those of the control area (p<0.05). On the correlation of the thresholds with current concentrations of Hgtotal in hair, directly proportional correlation was only observed for the thresholds of tactile sensation by Semmes-Weinstein monofilaments of lower lip (p-value<0.0001). It is concluded that mild changes in the sensitivity thresholds were predominant in the areas of exposure to methylmercury. Maintenance of exposure monitoring, guidance on public health measures and new clinical studies using somatosensory quantitative measures are required for clarification of the occurrence of clinical cases of poisoning in riparian areas contaminated by mercury.

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química.
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Nos últimos anos tem aumentado muito o uso de plantas medicinais na forma de chás, fitoterápicos e fitofármacos. A validação científica do efeito das plantas usadas na medicina popular, o controle de qualidade do material vegetal e dos fitoterápicos e a determinação de métodos ótimos de extração foram os pontos centrados como objetivo deste trabalho. As plantas estudadas foram: Wedelia paludosa, Adiantum cuneatum, Calendula officinallis e Equisetum arvense.

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The objective of this study was to standardize a quantitative technique to evaluate the in vitro capacity of agglutination of different mannanoligosaccharides (MOS) to the strain of Escherichia coli isolated from cases of infantile diarrhea in children from 0 to 5 years of age. The research for the expression of fimbria Type 1 present in the isolates was performed by the microhemoagglutination test. For the oligosaccharide agglutination assays three MOS markers were extracted from S. cerevisae, groups 1, 2 and 3, filtered through a microfilter, later diluted for surface sowing in chromogenic Agar E. coli. For microscopic evaluation of binder capacity of the MOS were subjected to slide agglutination tests. In order to estimate the total bacterial count (CBT), the counts of the three-plate set were calculated. Assumptions of homogeneity of variances and normality of data were validated, respectively, by the Levene and Shapiro-Wilk test. Homozygous variables were compared by analysis of variance in one way (ANOVA one-way), with contrasts by the Tukey method. Heterocedastic variables were compared with one-way ANOVA with application of the Welche contrast contrasts by the Games-Howell method. Correlations between CBTs, Titres hemagglutinants, diameters and areas of the globules were evaluated by the Pearson correlation test. All analyzes were conducted in software R, considering probability of error type 1 = 5% Of the 30 strains tested, 25 (83.3%) expressed hemagglutinating capacity with titers ranging from 1: 4 to 1: 16. The results suggest that the MOS showed effective action on the agglutination of the bacteria, since the estimates of CBTs of the strains treated with MOS were inferior the counts of the pure sample. The degree of agglutination may vary according to the composition of the MOS, since product 1 showed higher CBTs than the others, indicating that the agglutinated beads were not able to retain bacteria in the pores of the filters similarly to products 2 and 3. It was observed significant correlation between mannose-sensitive haemagglutination and MOS agglutination for products 1 and 2, suggesting that the intensity of bacterial agglutination may be related to the expression of type 1 fimbriae. It is concluded that the filtration and culture technique can be used to evaluate different degrees of agglutination of MOS products and the amount of bacteria retained in the filters appears to be more related to the expression of mano-sensitive type 1 fimbriae than to the sizes of the globules produced.
O objetivo deste estudo foi padronizar uma técnica quantitativa para avaliar a capacidade in vitro de aglutinação de diferentes mananoligossacarídeos (MOS) à cepa de Escherichia coli isoladas de casos de diarreia infantil, de crianças de 0 a 5 anos de vida. A pesquisa para a expressão da fímbria tipo 1 presente nos isolados foi realizada pelo teste de microhemoaglutinação. Para realização dos ensaios de aglutinação de oligossacarídeos utilizou-se três marcas comerciais de MOS, extraídos de S. cerevisae, grupos 1, 2 e 3, filtrados através de um microfiltro, posteriormente diluídos para semeadura superficial em Ágar cromogênico E. coli. Para avaliação microscópica da capacidade aglutinante do MOS foram submetidas a testes de aglutinação em lâmina.Para estimar a contagem bacteriana total (CBT), calculou-se a média das contagens do conjunto de três placas. Pressupostos de homogeneidade de variâncias e normalidade de dados foram validados, respectivamente, pelo teste de Levene e Shapiro-Wilk. Variáveis homocedásticas foram comparadas por análise de variância em uma via (ANOVA one-way), com contrastes pelo método de Tukey. Variáveis heterocedásticas foram comparadas com ANOVA one-way com aplicação da correção de Welche contrastes pelo método de Games-Howell. As correlações entre CBTs, Títulos hemaglutinantes, diâmetros e áreas dos glóbulos foram avaliados pelo teste de correlação de Pearson. Todas as análises foram conduzidas no software R, considerando-se probabilidade de erro tipo 1= 5%. Das 30 cepas testadas, 25 (83,3%) expressaram capacidade hemaglutinante com títulos variando entre 1:4 e 1:16. Os resultados sugerem que o MOS apresentou ação efetiva na aglutinação das bactérias, visto que as estimativas de CBTs das cepas tratadas com MOS foram inferiores as contagens da amostra pura. O grau de aglutinação pode variar segundo a composição do MOS, visto que o produto 1 apresentou CBTs superiores aos demais, denotando que os glóbulos aglutinados não foram capazes de reter bactérias nos poros dos filtros de forma similar aos produtos 2 e 3.Observou-se correlação significativa e negativa entre a hemaglutinação sensível à manose e aglutinação de MOS para os produtos 1 e 2, o que sugere que intensidade da aglutinação por bactérias pode estar relacionada a expressão de fímbrias do tipo 1. Conclui-se que a técnica de filtragem e cultura pode ser utilizada para avaliar diferentes graus de aglutinação de produtos a base de MOS e a quantidade de bactérias retidas nos filtros parece estar relacionada mais com a expressão de fímbrias tipo 1 mano-sensíveis do que com os tamanhos dos glóbulos produzidos.

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The objective of this study was to standardize a quantitative technique to evaluate the in vitro capacity of agglutination of different mannanoligosaccharides (MOS) to the strain of Escherichia coli isolated from cases of infantile diarrhea in children from 0 to 5 years of age. The research for the expression of fimbria Type 1 present in the isolates was performed by the microhemoagglutination test. For the oligosaccharide agglutination assays three MOS markers were extracted from S. cerevisae, groups 1, 2 and 3, filtered through a microfilter, later diluted for surface sowing in chromogenic Agar E. coli. For microscopic evaluation of binder capacity of the MOS were subjected to slide agglutination tests. In order to estimate the total bacterial count (CBT), the counts of the three-plate set were calculated. Assumptions of homogeneity of variances and normality of data were validated, respectively, by the Levene and Shapiro-Wilk test. Homozygous variables were compared by analysis of variance in one way (ANOVA one-way), with contrasts by the Tukey method. Heterocedastic variables were compared with one-way ANOVA with application of the Welche contrast contrasts by the Games-Howell method. Correlations between CBTs, Titres hemagglutinants, diameters and areas of the globules were evaluated by the Pearson correlation test. All analyzes were conducted in software R, considering probability of error type 1 = 5% Of the 30 strains tested, 25 (83.3%) expressed hemagglutinating capacity with titers ranging from 1: 4 to 1: 16. The results suggest that the MOS showed effective action on the agglutination of the bacteria, since the estimates of CBTs of the strains treated with MOS were inferior the counts of the pure sample. The degree of agglutination may vary according to the composition of the MOS, since product 1 showed higher CBTs than the others, indicating that the agglutinated beads were not able to retain bacteria in the pores of the filters similarly to products 2 and 3. It was observed significant correlation between mannose-sensitive haemagglutination and MOS agglutination for products 1 and 2, suggesting that the intensity of bacterial agglutination may be related to the expression of type 1 fimbriae. It is concluded that the filtration and culture technique can be used to evaluate different degrees of agglutination of MOS products and the amount of bacteria retained in the filters appears to be more related to the expression of mano-sensitive type 1 fimbriae than to the sizes of the globules produced.
O objetivo deste estudo foi padronizar uma técnica quantitativa para avaliar a capacidade in vitro de aglutinação de diferentes mananoligossacarídeos (MOS) à cepa de Escherichia coli isoladas de casos de diarreia infantil, de crianças de 0 a 5 anos de vida. A pesquisa para a expressão da fímbria tipo 1 presente nos isolados foi realizada pelo teste de microhemoaglutinação. Para realização dos ensaios de aglutinação de oligossacarídeos utilizou-se três marcas comerciais de MOS, extraídos de S. cerevisae, grupos 1, 2 e 3, filtrados através de um microfiltro, posteriormente diluídos para semeadura superficial em Ágar cromogênico E. coli. Para avaliação microscópica da capacidade aglutinante do MOS foram submetidas a testes de aglutinação em lâmina.Para estimar a contagem bacteriana total (CBT), calculou-se a média das contagens do conjunto de três placas. Pressupostos de homogeneidade de variâncias e normalidade de dados foram validados, respectivamente, pelo teste de Levene e Shapiro-Wilk. Variáveis homocedásticas foram comparadas por análise de variância em uma via (ANOVA one-way), com contrastes pelo método de Tukey. Variáveis heterocedásticas foram comparadas com ANOVA one-way com aplicação da correção de Welche contrastes pelo método de Games-Howell. As correlações entre CBTs, Títulos hemaglutinantes, diâmetros e áreas dos glóbulos foram avaliados pelo teste de correlação de Pearson. Todas as análises foram conduzidas no software R, considerando-se probabilidade de erro tipo 1= 5%. Das 30 cepas testadas, 25 (83,3%) expressaram capacidade hemaglutinante com títulos variando entre 1:4 e 1:16. Os resultados sugerem que o MOS apresentou ação efetiva na aglutinação das bactérias, visto que as estimativas de CBTs das cepas tratadas com MOS foram inferiores as contagens da amostra pura. O grau de aglutinação pode variar segundo a composição do MOS, visto que o produto 1 apresentou CBTs superiores aos demais, denotando que os glóbulos aglutinados não foram capazes de reter bactérias nos poros dos filtros de forma similar aos produtos 2 e 3.Observou-se correlação significativa e negativa entre a hemaglutinação sensível à manose e aglutinação de MOS para os produtos 1 e 2, o que sugere que intensidade da aglutinação por bactérias pode estar relacionada a expressão de fímbrias do tipo 1. Conclui-se que a técnica de filtragem e cultura pode ser utilizada para avaliar diferentes graus de aglutinação de produtos a base de MOS e a quantidade de bactérias retidas nos filtros parece estar relacionada mais com a expressão de fímbrias tipo 1 mano-sensíveis do que com os tamanhos dos glóbulos produzidos.

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Objective: The authors present the first study with the use of sodium fluorescein (SF) to enhance skull base tumors and performed a quantitative digital analysis of the tumors enhancement. The study intends to observe the grade of tumor enhancement by SF. Methods: A prospective experimental within-subjects study design was performed including six patients with skull base lesions. Digital pictures were obtained before and after the SF systemic injection, using the same light-source of the microsurgical field. The pictures were analyzed by software, which calculated the wavelength of the sodium fluorescein pre and post injection. Results: The group of tumors was composed as it follows: 1 vestibular schwannoma, 3 meningiomas, 1 craniopharyngioma and 1 pituitary adenoma. The SF enhancement in all tumors was strongly positive. The digital analysis of the pictures, considering the SF wavelength pre and post injection, presented p=0. 028 (Wilcoxon T test).Conclusions: The enhancement of the tumors by SF was consistent and evident. The introductory results suggest the possibility of using SF as an adjuvant tool for the skull base surgery. Further studies should test the clinical application of the SF in skull base tumors.
Objetivo: Os autores apresentam o primeiro estudo com o uso de Fluoresceína Sódica (FS) para contrastar tumores da base do crânio e realizam uma análise quantitativa digital do contraste tumoral. O estudo tem por objetivo observar o grau de contraste tumoral pela FS.Métodos: Foi realizado um estudo experimental prospectivo com controle intragrupo, incluindo seis pacientes com lesões da base do crânio. Fotografias digitais foram realizadas antes e após a administração sistêmica de FS, utilizando a mesma fonte de iluminação do campo microcirúrgico. As fotografias pré e pós injeção de FS foram analisadas por um software, o qual calculou o comprimento de onda da FS nas respectivas imagens. Resultados: O grupo de tumores foi constituído por: 1 schwanoma vestibular, 3 meningeomas, 1 craniofaringeoma e 1 adenoma de hipófise. O contraste dos tumores pela FS foi fortemente positivo. A análise digital das fotografias, considerando os comprimentos de onda pré e pós injeção de FS, apresentou p=0,028 (Teste T de Wilcoxon).Conclusões: O contraste dos tumores pela FS foi consistente. Os resultados introdutórios sugerem a possibilidade de uso da FS como uma ferramenta adjuvante para a cirurgia da base de crânio. Estudos complementares são necessários para definir aplicação clínica da FS em tumores da base do crânio.

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Most of ovine milk ´roduced worldwide is processed in dairy products, for this reason their quality is measured by rechnological properties, which are markedly affected by the composition, as well as the microbiological count. The objective of this study was to characterize rural properties that explore commercially milk sheep in the wester of the state of Santa Catarina by recording the production, composition an microbiological quality of the milk and the water used for the milking parlor. The experiment was conducted during august 2009 to june 2012 on tive farms. The animals used the experiment belonged to Milchschaf and Laucane breeds as wel their crosses, and crosses with beff breeds. Evaluations consisted in registration of production (ml/ewe/day), composition (fat, protein, lactose and minerais) an Somatic Cell Count (SCC) of milk, as well as the microbiological quality (total coliforms, Escherichia coli, mesophiles, salmonella sp., Listaria monocytogenes and Staphylococcus aureus) and microbiological quality of water (total coliforms, fecal coliforms and mesophiles) used for cleaning of milking equipment and utensils. For the assessment of milking, and then samples were separated and sent to and accredited laboratory. For the microbiological evaluation of milk the samples were collected directky from the cooling tank and the water obtained directly from the source to be evaluated in the Centro de diagnostic Microbiológico Animal (CEDIMA) of Centro de Ciências Agroveterinárais (CAV) at the Universidade do Estado de Santa Catarina (UDESC) for bacterial isolation. The results of the average daily milk production during the 150 days of lactation was 926.88 ml/ewe, while for the composition was 7.11% offat, 4.91% of protein, 4.52% of lactose, 17.81% of total solids and 490x10³/mlof SCC. The average results obtained by microbiological analysis of milk from ali sampling were 3535.29 x10³ CFU/ml for Standard Plate Count (SPC), 30x10³ CFU/ml for total coliforms, 12.12 CFU E. coli and 0.47x10³ CFU/ml for S. aureus, three isolates of Salmonella sp. And no isolates of Listeria monocytogenes. For water the average of ali properties was 76.31 x10³ CFU/ml for SPC, 37.82 NMP/100 ml for total coliforms and no isolates of fecal coliforms. Data of production, composition and microbiological were statistically analyzed using the GLM procedure (General Linear Model) of the SAS statistically analyzed using the GLM procedure (General Linear Model) of the SAS statistically package (SAS Institute, 2005). SCC data were previously transformed into a logarithm base 10. The study allowed to characterize the ovine milk as well the microbiological water quality of these properties. The results for microbiological contamination of milk and water did not correspond with the limits established by Brazilian legislation compared with cow s milk and water consumption, however, as for the evaluation of milk production and compositional, these data can guidance for those involved in the activity and useful for industry that absorb the production of ovine milk in the region ultin further research is done
A maior parte do leite ovino produzido no mundo é transformado em produto lácteos, por esta raz!lo a qualidade deste é medida principalmente pelas sua propriedades tecnológicas, que são marcadamente afetados pela composição assim como pela sua qualidade microbiológica. O objetivo deste trabalho fo caracterizar as propriedades rurais que exploravam comercialmente o leite ovino n região oeste do estado de Santa Catarina quanto a sua produção, composição qualidade microbiológica do leite e da água utilizada para a higienizaçao d equipamentos. O experimento foi conduzido entre os meses de agosto de 2009 junho de 2012 em cinco propriedades rurais. Os animais utilizados no experimento pertenciam às raças Milchschaf, Lacaune e suas cruzas, além de cruzamentos co raças de corte. As avaliações consistiram no registro da produçao (mUovelha/dia) composição (gordura, proteína, lactose e minerais) e Contagem de Célula Somáticas (CCS) do leite, assim como a qualidade microbiológica (Coliformes totais Escherichia co/i, Mesófilos, Sa/mone//a sp., Usteria monocytogenes Staphylococcus aureus) deste e a qualidade microbiológica da água (Coliforme totais, Coliformes termotolerantes e Mesófilos) utilizada para a higienização do equipamentos e utensílios de ordenha. Para a avaliação da produção e composiçã o leite foi coletado no momento da ordenha, em seguida uma amostra era separad e enviada para laboratório credenciado. Para a avaliação microbiológica as amostra de leite foram coletadas diretamente do tanque de resfriamento e a água obtid diretamente da fonte, para serem avaliadas no Centro de Diagnóstico Microbiológic Animal (CEDIMA) do Centro de Ciências Agroveterinárias (CAV) da Universidade d Estado de Santa Catarina (UDESC) para isolamento bacteriano. Os resultados d produção média diária de leite durante os 150 dias de lactação foi de 926,8 mL/ovelha, enquanto que para a composição foi de 7,11% de gordura, 4,91% d proteína, 4,52% de lactose, 17,81% de sólidos totais e 490x103 CCS/mL. As média dos resultados obtidos através das análises microbiológicas do leite de todas a coletas foram de 3.535,29x103 UFC/mL para CPP totais, 12,12 UFC/mL para E. co/i e 0,47x103 30x103 UFC/mL para Coliforme UFC/mL para S. aureus, trê isolamentos de Sa/mone//a sp. e ausência de Usteria monocytogenes. Para a águ utilizada nas propriedades as médias entre todas as propriedades foi de 76,31x10 UFC/mL para CPP, 37,82 NMP/100mL para Coliformes totais e ausência d Coliformes termotolerantes. Os dados de produção, composição e microbiológico foram submetidos a análise estatística utilizando-se o procedimento GLM (Genera Linear Model) do pacote estatístico SAS (SAS INSTITUTE, 2005). Os dados de CCS foram previamente transformadas para logaritmo de base 10. O estudo permiti caracterizar o leite ovino assim como a qualidade microbiológica da água desta propriedades. Os resultados para a contaminaçao microbiológica do leite e da água não corresponderam com os limites estabelecidos pela legislação brasileira quand comparados com o leite bovino e para a água de consumo, entretanto, assim com para a avaliação produtiva e composicional do leite, estes dados podem servir d subsídio para os envolvidos na atividade e úteis para a indústria que absorve produção de leite ovino da região até que novas pesquisas sejam realizadas

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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
The dissertation is divided into two chapters, the first one is a bibliographical review about urinary lithiasis in felines and the second chapter a scientific article reporting epidemiological, clinical and laboratory characterization of urolithiasis in felines. Urinay calculi of 42 felines attended in Veterinary teaching Hospital of Federal University of Goias (HV/EVZ/UFG) and other private veterinary clinics and hospitals were assessed using chemical analysis and energy dispersive spectroscopy (EDS). The most observed mineral was struvite (38,1%), followed by ammonium urate (35,7%) and calcium oxalate (26,2%). The males were more affected (26/42), as well mixedbreed animals (36/42). Animals aged between 25 and 72 months old were the most affected (27/42). In 33 cases (78,6%) the stones were recovered of bladder. The clinical signs with most occurrence were dysuria (65,0%), hematuria (50,0%), vomiting (17,5%) and anorexia (12,5%). Of the 42 felines studied, 39 (92.8%) were neutered. Regarding feeding, 26 (61.9%) cats received dry rations exclusively, while 13 (38.1%) received dry and wet rations. Despite the higher occurrence of struvite uroliths, a significant presence of ammonium urate uroliths was observed, which highlights the importance of studies on feline disease. The urolithiasis in cats is little studied in our country and the present work is a pioneer in the analysis of calculations in felines in Brazil, mainly due to the use of techniques of quantitative analysis, such as the dispersive energy spectroscopy.
A dissertação está dividida em dois capítulos, sendo o primeiro uma revisão bibliográfica sobre a litíase urinária em felinos e o segundo capítulo um artigo científico onde objetivou-se caracterizar epidemiológica, clínica e laboratorialmente a urolitíase em felinos. Cálculos urinários de 42 gatos atendidos no Hospital Veterinário da Escola de Veterinária e Zootecnia da Universidade Federal de Goiás (HV/EVZ/UFG) e em clínicas e hospitais veterinários de diferentes regiões do país foram analisados por meio de técnica de análise química, e espectroscopia de energia dispersiva (EDS). A estruvita foi o mineral mais observado (38,1%), seguido de urato amônio (35,7%) e oxalato de cálcio (26,2%). Os machos foram mais acometidos (26/42), bem como os animais sem raça definida (36/42). Animais com idade entre 25 e 72 meses tiveram maior representação (27/42). Em 33 casos (78,6%) os cálculos foram recuperados da bexiga. Os sinais clínicos de maior ocorrência foram disúria (65,0%), hematúria (50,0%), vômito (17,5%) e anorexia (12,5%). Dos 42 felinos estudados, 39 (92,8%) eram castrados. Quanto a alimentação, 26 (61,9%) gatos recebiam exclusivamente ração seca, enquanto que 13 (38,1%) recebiam associação de ração seca e úmida. Apesar da maior ocorrência de urólitos de estruvita, foi observada significativa presença de urólitos de urato amônio o que ressalta a importância de estudos sobre a enfermidade na espécie felina. A urolitíase em gatos é pouco estudada em nosso país e o presente trabalho é pioneiro na análise de cálculos em felinos no Brasil, especialmente pelo uso de técnicas de análise quantitativa, como a espectroscopia de energia dispersiva.

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The Curraleiro cattle are extremely docile and resistant to infectious diseases and parasites. They may be used in exploration of low-quality pastures, without great investments, when other breeds could show a low productivity or even survival difficulties. This genetic potential runs risk to extinction due to its replace by more productive breeds. The Curraleiro cattle resistence to illness is popularly known and many works has been published about it, although its immunologic system physiology is completely unknown. Such features are plausible reasons for the preservation of this potentially genetic resource. So, the mean aim of this study was to establish an immunological profile by marking and quantification of T and B lymphocytes in Curraleiro breed with immunocytochemistry. Thus, it was used 116 bovines, male and female, with different ages from two farms situated at Goiás State, Brazil. The animals were allotted in groups according to age, sex and origin. Blood samples were collected and processed in accordance with immunocytochemistry standard technique using lymphoid markers species-specific, anti-CD3 (MM1A BoCD3) and anti-LB (LCTB16A clone B-B14), for T and B lymphocytes counting, respectively. All procedures were accomplished at Veterinary School, Federal University of Goiás, Brazil. The data were submitted to descriptive statistics and then to Kruskall Wallis and Mann-Whitney tests. The results showed decreased levels of leukocytes, lymphocytes, T lymphocytes and B lymphocytes along the age advance. Absolute values of leukocytes, lymphocytes and T lymphocytes were higher in males than females. None of the evaluated parameters were affected by differences of the management carried out at two farms.
O gado Curraleiro é extremamente dócil, resistente às doenças e parasitas, que pode ser utilizado, sem grandes investimentos na exploração de pastagens naturais de baixa qualidade onde outras raças teriam baixa produtividade ou até mesmo dificuldades de sobrevivência. Todo esse potencial genético encontra-se em sério risco de extinção, uma vez que esses animais vêm sendo substituídos por outros com maior produtividade. A resistência do Curraleiro às enfermidades é popularmente conhecida e divulgada, porém desconhece-se por completo a fisiologia do sistema imunológico desses animais. Estas características são notáveis justificativas para conservar este recurso genético potencialmente importante. Assim, este estudo teve por objetivo traçar um perfil imunológico, através de marcação imunocitoquímica e quantificação de linfócitos T e B em bovinos da raça Curraleiro. Para tal, foram utilizados 116 animais entre machos e fêmeas, de diferentes faixas etárias, provenientes de duas propriedades de criação de gado Curraleiro do Estado de Goiás, sendo alocados em grupos conforme a faixa etária, sexo e origem. As amostras de sangue foram colhidas e processadas de acordo com o padrão da técnica de imunocitoquímica e posteriormente utilizados os marcadores linfóides espécieespecíficos, anti-CD3 (MM1A BoCD3) e anti-LB (LCTB16A clone B-B14), para a quantificação de linfócitos T e linfócitos B, respectivamente. Todo procedimento foi realizado na Escola de Veterinária da UFG. Inicialmente os dados foram submetidos à estatística descritiva e posteriormente ao teste de Kruskall Wallis e Mann-Whitney. Com o avançar da idade, diminuíram-se os níveis de leucócitos, linfócitos, linfócitos T e linfócitos B. Os valores absolutos de leucócitos, linfócitos e linfócitos T foram maiores nos machos em relação às fêmeas. Nenhum dos parâmetros avaliados sofreu influência em relação à diferença de qualidade de manejo nas duas propriedades.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
To fill some gaps on intrinsic mechanisms of the biology of the oviposition and embryogenesis of R. (B.) microplus and R. (R.) sanguineus, was evaluated the variability protein in eggs per day of posture and incubation. For this, engorged female laid eggs in controlled environment chamber (27 ? 1oC, 80 ? 5% UR, and darkness). As soon as the female initiated the oviposition, egg samples of 50 mg was collected daily, conditioned in eppendorf tube and preserved in freezer - 20?C, characterizing the period of posture. Samples of 50 mg was removed from a fresh egg mixture and put in perforated eppendorf tube, kept in environment chamber (27 ? 1oC, 80 ? 5% UR, and darkness). Daily, one tube was transferred to freezer -20?C until the first larva hatch. Thus a sequence of different stage of embryogenesis was obtained. The Bradford method was used to measure the protein concentration and subsequently, the electrophoresis profiles was performed in SDS-PAGE. The protein concentrations was correlated with the oviposition and embryogenesis days using the Pearson (r) correlation and for this, the data was transformed in logarithmic value [log (X+1)] after the normality to be discarded (test of Shapiro-Wilk). During oviposition the protein concentrations of the eggs of R. (B.) microplus and R. (R.) sanguineus remained constant until the last days when abrupt increase was observed. In both of species, variation in the concentration of protein was observed during all embryonic period. The number of detectable bands of proteins decreasing during oviposition and embryogenesis days, but in the last days a new band was found. It can inferred that the proteins variation in the eggs of R. (B.) microplus and R. (R.) sanguineus is correlated with the days oviposition and incubation. The ticks R. (B.) microplus and R. (R.) sanguineus have a different oviposition profile proteins model that can be use as phenetic feature. As well, a different way of degradation of protein for each species was characterized.
Objetivando preencher algumas lacunas sobre mecanismos intr?nsecos da biologia da oviposi??o e embriog?nese de R. (B.) microplus e R. (R.) sanguineus, foi avaliada a variabilidade prot?ica dos ovos por dia de postura e incuba??o. Para tal, f?meas ingurgitadas foram colocadas para efetuar postura em estufa biol?gica sob condi??es controladas (27 ? 1oC, 80 ? 5% UR, escotofase). Ap?s in?cio da postura, amostras di?rias de 50 mg de ovos foram coletadas, acondicionadas e preservadas a 20?C, caracterizando o per?odo de postura. A partir de um pool de ovos rec?m colocados, foram obtidas al?quotas de 50 mg que acondicionadas em tubos de eppendorf perfurados foram mantidas em estufa biol?gica nas mesmas condi??es controladas descritas acima. Desde a separa??o das al?quotas at? o surgimento da primeira larva, diariamente uma amostra foi transferida para freezer ? -20?C, obtendo-se assim ovos seq?encialmente em diferentes momentos da embriog?nese. Para dosagem das prote?nas utilizou-se o m?todo de Bradford, e os perfis eletrofor?ticos foram tra?ados atrav?s de eletroforese em gel de poliacrilamida. Os dados das concentra??es prot?icas foram correlacionados com os dias de postura e de embriog?nese. Para isso, utilizou-se o coeficiente de correla??o de Pearson (r), com os dados da concentra??o transformados logar?timicamente [log (X+1)]. Os dados foram transformados ap?s o descarte da normalidade (teste de Shapiro-Wilk). De modo geral as concentra??es das prote?nas nos ovos de R. (B.) microplus e R. (R.) sanguineus durante a postura mantiveram-se constantes at? os ?ltimos dias quando se observou aumento abrupto das concentra??es. Nas duas esp?cies, foram observadas varia??es nas concentra??es das prote?nas durante o per?odo embrion?rio. Ainda em ambas esp?cies, na an?lise das bandas prot?icas, o n?mero de bandas detect?veis diminuiu ao longo do per?odo de postura e embriog?nese, sendo observado nos ?ltimos dias surgimento de uma nova banda. Pode-se depreender que a varia??o na concentra??o das prote?nas dos ovos de R. (B.) microplus e R. (R.) sanguineus est? correlacionada com os dias de postura e incuba??o, atrav?s do aumento na concentra??o de prote?nas ? medida que o final da postura e eclos?o da larva se aproximam. Devido ?s diferen?as entre os perfis prot?icos de R. (B.) microplus e R.(R.) sanguineus ao longo dos dias de postura, conclui-se que as prote?na s disponibilizadas aos ovos durante o per?odo de postura s?o diferentes entre estas duas esp?cies e que os zimogramas podem ser utilizados como marcadores fen?ticos. Ainda pode-se concluir que, ao longo da embriog?nese, devido ao desaparecimento e surgimento de bandas prot?icas, as prote?nas dispon?veis para o embri?o de R. (B.) microplus e R.(R.) sanguineus s?o biotransformadas de modo que h? um perfil de degrada??o particular para cada esp?cie.

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Objetivo: Os autores apresentam o primeiro estudo com o uso de Fluoresce?na S?dica (FS) para contrastar tumores da base do cr?nio e realizam uma an?lise quantitativa digital do contraste tumoral. O estudo tem por objetivo observar o grau de contraste tumoral pela FS. M?todos: Foi realizado um estudo experimental prospectivo com controle intragrupo, incluindo seis pacientes com les?es da base do cr?nio. Fotografias digitais foram realizadas antes e ap?s a administra??o sist?mica de FS, utilizando a mesma fonte de ilumina??o do campo microcir?rgico. As fotografias pr? e p?s inje??o de FS foram analisadas por um software, o qual calculou o comprimento de onda da FS nas respectivas imagens. Resultados: O grupo de tumores foi constitu?do por: 1 schwanoma vestibular, 3 meningeomas, 1 craniofaringeoma e 1 adenoma de hip?fise. O contraste dos tumores pela FS foi fortemente positivo. A an?lise digital das fotografias, considerando os comprimentos de onda pr? e p?s inje??o de FS, apresentou p=0,028 (Teste T de Wilcoxon). Conclus?es: O contraste dos tumores pela FS foi consistente. Os resultados introdut?rios sugerem a possibilidade de uso da FS como uma ferramenta adjuvante para a cirurgia da base de cr?nio. Estudos complementares s?o necess?rios para definir aplica??o cl?nica da FS em tumores da base do cr?nio.

Introduzione Grazie al globale miglioramento delle cure e delle condizioni di vita, la popolazione mondiale sta sempre più invecchiando tuttavia come si evince dalla letteratura il bisogno di rendere migliore lo stato qualitativo di questo processo necessità di ulteriori sviluppi in ricerca. Il termine fragilità identifica una condizione di vulnerabilità provocata dall’incapacità dei sistemi biologici, a vari livelli, di conservare indenni le riserve funzionali di organi e apparati che regolano la vita della persona. L’anziano, per motivi legati al processo d’invecchiamento e alle malattie intercorrenti, diviene più vulnerabile e molte condizioni possono alterare l’equilibrio omeostatico dell’organismo. La fragilità è provocata dall’incapacità dei sistemi biologici, a vari livelli (dalla cellula alla persona), di conservare l’omeostasi . Con l’invecchiamento si assiste alla riduzione delle riserve funzionali di organi e di apparati soprattutto per quanto concerne l’apparato muscolo-scheletrico, che espongono l’individuo a un maggior rischio di “rottura” e di “frattura” indotto da agenti patogeni o da modificazioni dell’equilibrio bio-psicologico e della qualità di vita. Poiché le determinanti di questo processo sono molto diverse (biologico-cliniche o ambientali), è talvolta difficile identificare la fragilità e i suoi fattori scatenanti, sui quali intervenire, in senso sia preventivo sia terapeutico. Le persone molto anziane rappresentano la fascia d’età maggiormente coinvolta dai meccanismi che inducono fragilità , perché la condizione clinica caratterizzata da disabilità, conseguente alle patologie croniche, è spesso apparentemente indistinguibile dalle condizioni di fragilità stessa . Quest’ultima, quindi, si definisce meglio dall’insieme di molte variabili piuttosto che da una singola entità, motivo per il quale è difficile fornirne una definizione precisa. I criteri diagnostici per definire la osteosarcodinapenia , hanno indicato come possibili marker la presenza di disturbi dell’equilibrio e della marcia, la sarcopenia, la ridotta tolleranza allo sforzo, le modificazioni della composizione corporea e dell’aspetto quantitativo e qualitativo del tessuto osseo (perdita di peso, sarcopenia, malnutrizione ). I criteri sono stati validati da una serie di studi che hanno dimostrato l’associazione di queste caratteristiche con l’aumento di rischio di istituzionalizzazione e di morte, nonché con l’insorgenza di sindromi geriatriche (disabilità, stato cognitivo, cadute, incontinenza urinaria, malnutrizione ). Identificare e comprendere il ruolo della fragilità come condizione che modula la qualità e la durata della vita dell’anziano costituisce un importante punto di partenza; in quest’ottica, infatti, essa diviene target d’interventi mirati sul piano clinico, chirurgico, psicologico e sociale per ridurre il rischio di eventi negativi. Riconoscere quindi le caratteristiche biologiche della osteosarcodinapenia età-correlata e comprendere le sue determinanti fisiopatologiche sono stati al centro della ricerca gerontologica degli ultimi anni. In particolare la ricerca si è concentrata sull’identificazione di marcatori biologici che permettano uno screening della fragilità in fase precoce quando le possibilità di prevenzione e di intervento hanno maggiore probabilità di successo. Come già indicato dalla letteratura l’attenzione verte principalmente sui problemi fisici indotti dalla fragilità: -riduzione del patrimonio minerale osseo quantitativo (Valutazione della BMD [Bone Mineral Density ] tramite metodica DXA [Dual X-ray Absorptiometry] e qualitativo (valutabile mediante metodica TBS [Trabecular Bone Score]);-disabilità; aumentata vulnerabilità clinica;-elevato rischio di deterioramento muscolo-scheletrico (stato di malattia osteoporotica; stato sarcopenico valutabile con metodica Total Body Scan iDXA for Metabolic Health);-Riduzione del grado di stato funzionale sulla base della CGA (Comprehensive Geriatric Assessment) ossia la metodologia della Valutazione Multidimensionale (VMD) è considerata un valido strumento della medicina geriatrica che lo ha elaborato e validato; esso non si limita al solo momento valutativo-diagnostico ma dal punto di vista operativo si estende anche alla gestione del paziente. Essendo l’interdisciplinarità l’elemento caratterizzante la VMD, risulta un valido strumento di indagine nei confronti dell’anziano fragile.Risulta quindi evidente che l’elemento essenziale è la multidimensionalità che la valutazione clinica deve avere.[1-13] Obiettivi.Gli obiettivi di questo studio sono stati di esaminare le associazioni tra i parametri cognitivi neuro-motori e nutrizionale e la densità minerale ossea, la qualità dell’osso, la massa grassa , la massa magra in tutto il corpo in pazienti geriatrici protesizzati d’anca,divisi in due gruppi a seconda della terapia per l’osso con Denosumab (DMAB) vs Alendronato (ALD) e nei controlli sani (CNT) di riferimento. Materiali e Metodi. Sono stati arruolati 95 pazienti (età media 80±8 anni) protesizzati d’anca e 50 controlli sani di pari età (età media 74±11anni). La popolazione di studio è stata divisa in due gruppi a seconda della terapia con Denosumab (DMAB) vs Alendronato (ALD) . Sono state effettuate le scale di valutazione Geriartrica dello stato funzionale (CGA):HAND GRIP ,BARTHEL index, ADL,IADL,MNA,CIRS com, CIRS sev, Tinetti, MMSE. La Densità minerale ossea (BMD, g/cm2) a livello del rachide lombare (L1-L4) e dell’intero del femore è stata misurata mediante il densitometro DXA Lunar Prodigy (GE Lunar , Madison, WI, USA) cosi come la valutazione del corpo metabolico totale espresso dall’ Indice di massa scheletrica relativa (RSMI). Per tutti i soggetti è stato calcolato l’indice di massa corporea (BMI, kg/m2). Secondo l’equazione antropometrica [14], la sarcopenia è stata definite da RSMI<5.5 kg/m2 nelle donne. Il valore di TBS è stato calcolato su tutti gli esami densitometrici del rachide lombare utilizzando il TBS iNsight Medimaps software (Lunar Prodigy). Valutazione del rischio fratturativo atteso nei 10 anni successivi in rapporto ai fattori di rischio riconosciuti (analisi algoritmo FRAX).Tutti i pazienti sono stati sottoposti al dosaggio sierico della 25 idrossivitamina D (25(OH)D ng/ml),del Paratormone PTH pg/ml e valutazione dell’ emoglobina Hb g/L. Risultati.Nei 95 pazienti arruolati si osservava una riduzione di massa ossea per 78 pazienti (80%); in particolare 52 in condizione di osteoporosi (53%) e 41 (42%) di osteopenia. I valori di BMD sono risultati significativamente più ridotti nei pazienti protesizzati d’anca rispetto al gruppo di controllo (rispettivamente, rachide lombare: 0.998±0.161 g/cm2 vs 1.240±0.932 g/cm2;Collo del femore: 0.784±0.212 g/cm2 vs 0.845±0.164 g/cm2; Ward 0.563±0.173 g/cm2 vs 0.657±0.106 g/cm2; Trocantere: 0.666 ±0.104 g/cm2 vs 0.725±0.143 g/cm2;Femore Intero: 0.827±0.182 g/cm2 vs 1.033±0.161 g/cm2, entrambi con p<0.001). Ad Oggi (rispettivamente, rachide lombare: 1.178±0.761 g/cm2 Collo del femore: 0.989±0.712 g/cm2; Ward 0.874±0.982 g/cm2; Trocantere: 0.981 ±0.382 g/cm2;Femore Intero: 1.036±0.294 g/cm2).I valori di TBS a livello del rachide lombare sono risultati significativamente più bassi nei pazienti protesizzati nei confronti del gruppo di controllo (rispettivamente, 1.012±0.163 score vs 1.361±0.126 score, entrambi con p<0.001).Ad Oggi I Valori RSMI medi sono 5,42±0,078kg/m² al di sotto della media della popolazione di controllo (5,7 Kg/m²) incrementati in media di 2,07±0,078kg/m² rispetto al T0. Tra I livelli di TBS e i livelli di RSMI rispettivamente 1.914±0.152 e 4,72±0,029kg/m² si denota una correlazione positiva con p<0.001; con un’implementazione media del TBS dal T0 dello 0,874±0.121.Da un confronto dei dati ad 1 anno sui 55 pazienti conclusi risulta che i livelli di TBS sembrano influenzati dalla terapia antiriassorbitiva; il miglioramento risulta maggiormente nel gruppo ALD(60%) rispetto al gruppo DMAB (40%); in entrambi i casi il miglioramento non supera il 5-8% di significatività totale percui non statisticamente rilevabile. I dosaggi della 25(OH)D sono risultati 13±1.4 ng/ml al T0 e 24±0.7 ng/ml a T1. I Valori del PTH sono risultati 40,36±2.7 pg/ml al T0 e 47±2.7 pg/ml al T1.I Valori dell’Hb sono risultati 12,47±1.1 g/L al T0e 14,18±0.97 g/L al T1. Dall’analisi dei parametri geriatrici rispettivamente nel gruppo ALD vs DMAB abbiamo riscontrato: Hand-grip strength, Kg ± DS Nelle pazienti donne :15.3 ± 5.3 vs 13.5 ± 6.2 ,nei pz uomini 22.1 ± 5.0 vs 23.2 ± 1.6; Barthel Index, score ± DS 91 ± 14 vs 83 ± 23;ADL, n° ± DS 5.5 ± 0.9 vs 5.1 ± 1.5 ;IADL, n° ± DS 5.8 ± 2.5 vs5.1 ± 3.4 ;MNA, score ± DS 11.4 ± 2.2 vs 10.4 ± 2.9 CIRS comorbidity, score ± DS 4.3 ± 1.8 vs4.2 ± 1.6 ;CIRS severity, score ± DS 1.9 ± 0.5 vs 1.9 ± 0.3 ,SPMSQ, score ± DS 2.0±2.2 vs 1.9 ± 2.1 ; BMI, media ± DS 24.4 ± 5.2 vs21.3 ± 2.9 Esaminando le caratteristiche basali dal punto di vista osseo e muscolare si evidenzia innanzitutto uno stato carenziale di Vitamina D comune ai due gruppi. In entrambi la BMD è indicativa di osteoporosi a livello del collo femorale ed osteopenia a livello della colonna (verosimilmente per gli artefatti dovuti alla presenza di osteoartrosi e/o fratture vertebrali). Il TBS presenta una lieve differenza tra i due gruppi (DMab 1.129 ± 0.160 ALD 1.032 ± 0.162, p .073), indicando in entrambi una condizione di degradazione ossea. Considerando i valori Hand Grip e di RSMI, con riferimento ai cut off indicati nel Consensus EWGSOP2, in entrambi i gruppi si denota uno stato di sarcopenia “confermata”. In particolare, i valori di RSMI nelle donne sono francamente patologici, mentre quelli degli uomini sono ai limiti inferiori (Ald 7,7 ± 1,2, Dmab 7,1± 0,1), ma dobbiamo pesare la prevalenza inferiore del sesso maschile all’interno del campione (12,2%).Non sussiste una reale differenza tra i due farmaci, neppure dopo aggiustamento per le variabili (BMI e TBS).Le variazioni percentuali dell’RSMI mostrano chiaramente un effetto di potenziamento della muscolatura appendicolare da parte di Denosumab, con differenza statisticamente significativa rispetto ad Alendronato (Ald -5.8 ± 12.4 vs Dmab 0.5 ± 4.5, p=0.046) Conclusioni. Attualmente lo studio ci indica come vi sia una correlazione tra il recupero della massa muscolare la riduzione della massa grassa e il recupero funzionale ,motorio e sull’indice di fragilità.Questo studio mostra come la sarcopenia sia frequente nei pazienti anziani, per lo più in quelli classificati come normali o in sovrappeso secondo il BMI. Pertanto i valori di TBS e BMD, potrebbero avere un ruolo chiave in un feedback muscolo-osso nel paziente geriatrico in stato post-operatorio come quello della protesi d’anca. I pazienti che riportano frattura di femore da fragilità sono soggetti osteosarcopenici dobbiamo considerare la sindrome, non le singole patologie.La BMD e il TBS ad un anno dalla frattura mostrano un bilancio “in perdita”, nonostante la prescrizione di terapia anti-riassorbitiva, verosimilmente legato alla transitoria immobilizzazione successiva all’evento indice che si debba raccomandare ed incoraggiare la prosecuzione della terapia oltre il 1°anno, in associazione ad interventi mirati a favorire la mobilizzazione del paziente.Coerentemente ai dati risultanti ,in associazione ad un aumento medio della 25(OH)D, si osserva nei pazienti più complianti un recupero maggiormente marcato anche sulla BMD ,specchio della quantità minerale ossea, minore invece è il recupero sulla qualità dell’osso mostrata dall’analisi dell’osso trabecolare (TBS).Il Denosumab sembra avere un potenziale effetto di rinforzo muscolare, per cui sembra essere un promettente approccio al paziente anziano osteosarcopenico. Il TBS in associazione alla valutazione del corpo metabolico totale ,si dimostrano parametri clinici aggiuntivi rispetto ai valori densitometrici standard sul nostro campione di pazienti anziani ,suggerendo come queste metodiche possano migliorare la valutazione di “fragilità” del paziente geriatrico nel post-fratturativo per migliorarne l’inquadramento diagnostico-terapeurico e una migliore compliance alla terapia. Bibliografia 1.Rockwood K et al.Interdiscip Top Gerontol Geriatr. 2015;41:VII-X.;2.Chen KW et al.Worldviews Evid Based Nurs. 2017 Apr 27 3.Mitnitski AB et al. Biogerontology. 2017 Mar 2. ;4.Searle SD, Rockwood K. et al. Alzheimers Res Ther. 2015 Aug 3;7(1):54. 5.Strawbridge WJ et al.Med S ci 1998;53A:M9-16.;6.Chin A et al.J Clin Epidemiol 1999;52:1015-21.;7.Walston J et al. J Am Geriatr S oc 2006;54:991-1001.;8.Rantanen T et al.J Gerontol A Biol Med Sci 2000;55A:M168-73.;9.Rantanen T et al.J Am Geriatr S oc 2000;48:613-7.;10.Rozzini R et al.Arch I ntern Med 2001;161:299-300.;11.Brown JC et al.Aging Clin Exp Res. 2016 Mar 28 12.Villa P et al.J Endocrinol Invest. 2016 Feb;39(2):191-8..;13.Lamy O et al.Rev Med Suisse. 2011 Nov 2;7(315):2130, 2132-4, 2136.;14.Baumgartner RN et al., J Epidemiol. 147:755–76
Introduction Thanks to the global improvement in care and living conditions, the world population is increasingly aging, however, as evidenced by the literature, the need to improve the qualitative state of this process requires further developments in research. The term fragility identifies a condition of vulnerability caused by the inability of biological systems, at various levels, to preserve the functional reserves of organs and systems that regulate a person's life unscathed. The elderly, for reasons related to the aging process and intercurrent illnesses, become more vulnerable and many conditions can alter the body's homeostatic balance. Fragility is caused by the inability of biological systems, at various levels (from cell to person), to maintain homeostasis. With aging there is a reduction in the functional reserves of organs and systems, especially as regards the musculoskeletal system, which expose the individual to a greater risk of "rupture" and "fracture" induced by pathogens or by changes in the bio-psychological balance and quality of life. Since the determinants of this process are very different (biological-clinical or environmental), it is sometimes difficult to identify fragility and its triggering factors, on which to intervene, both preventively and therapeutically. The very elderly represent the age group most involved in the mechanisms that induce fragility, because the clinical condition characterized by disability, resulting from chronic diseases, is often apparently indistinguishable from the conditions of fragility itself. The latter, therefore, is better defined by the set of many variables rather than by a single entity, which is why it is difficult to provide a precise definition. The diagnostic criteria for defining osteosarcodynapenia have indicated as possible markers the presence of balance and gait disorders, sarcopenia, reduced exercise tolerance, changes in body composition and in the quantitative and qualitative aspect of bone tissue (loss weight, sarcopenia, malnutrition). The criteria have been validated by a series of studies that have shown the association of these characteristics with the increased risk of institutionalization and death, as well as with the onset of geriatric syndromes (disability, cognitive status, falls, urinary incontinence, malnutrition). Identifying and understanding the role of frailty as a condition that modulates the quality and duration of life of the elderly is an important starting point; from this point of view, in fact, it becomes the target of targeted interventions on a clinical, surgical, psychological and social level to reduce the risk of negative events. Therefore, recognizing the biological characteristics of age-related osteosarcodynapenia and understanding its pathophysiological determinants have been at the center of gerontological research in recent years. In particular, the research focused on the identification of biological markers that allow screening of frailty at an early stage when the possibilities of prevention and intervention are more likely to be successful. As already indicated in the literature, the focus is mainly on physical problems induced by fragility: - quantitative reduction in bone mineral stock (BMD [Bone Mineral Density] assessment by DXA [Dual X-ray Absorptiometry] and qualitative method (assessable by TBS [Trabecular Bone Score] method)); - disability; increased clinical vulnerability; -high risk of musculoskeletal deterioration (osteoporotic disease state; sarcopenic state assessable with the Total Body Scan iDXA for Metabolic Health method); - Reduction of the degree of functional state based on the CGA (Comprehensive Geriatric Assessment) or the Multidimensional Assessment (VMD) methodology it is considered a valid tool of geriatric medicine that elaborated and validated it; it is not limited only to the evaluation-diagnostic moment but from an operational point of view it also extends to the management of the patient. Since interdisciplinarity is the characterizing element of the VMD, is a valid investigation tool for the frail elderly. It is therefore evident that and the essential element is the multidimensionality that clinical evaluation must have. [1-13] OBJECTIVES: The objectives of this study were to examine the associations between neuro-motor and nutritional cognitive parameters and bone mineral density, bone quality, fat mass, and lean body mass in prosthetic geriatric patients. hip, divided into two groups according to bone therapy with Denosumab (DMAB) vs Alendronate (ALD) and in the reference healthy controls (CNT) Materials and methods: 95 patients (mean age 80 ± 8 years) with hip replacement and 50 healthy controls of the same age (mean age 74 ± 11 years) were enrolled. The study population was divided into two groups according to Denosumab (DMAB) vs Alendronate (ALD) therapy. The Geriartric assessment scales of functional status (CGA) were performed: HAND GRIP, BARTHEL index, ADL, IADL, MNA, CIRS com, CIRS sev, Tinetti, MMSE. Bone mineral density (BMD, g / cm2) at the level of the lumbar spine (L1-L4) and of the entire femur was measured by the DXA Lunar Prodigy densitometer (GE Lunar, Madison, WI, USA) as well as the evaluation of the total metabolic body expressed by the Relative Skeletal Mass Index (RSMI). The body mass index (BMI, kg / m2) was calculated for all subjects. According to the anthropometric equation [14], sarcopenia was defined by RSMI <5.5 kg / m2 in women. The TBS value was calculated on all lumbar spine densitometric examinations using the TBS iNsight Medimaps software (Lunar Prodigy). Evaluation of the expected fracture risk in the next 10 years in relation to the recognized risk factors (FRAX algorithm analysis) All patients underwent a serum dosage of 25 hydroxyvitamin D (25 (OH) D ng / ml), of the PTH pg parathyroid hormone / ml and evaluation of hemoglobin Hb g / L. RESULTS: In the 95 patients enrolled, a reduction in bone mass was observed for 78 patients (80%); in particular 52 with osteoporosis (53%) and 41 (42%) with osteopenia. BMD values ​​were significantly lower in hip replacement patients than in the control group (respectively, lumbar spine: 0.998 ± 0.161 g / cm2 vs 1.240 ± 0.932 g / cm2; Femoral neck: 0.784 ± 0.212 g / cm2 vs 0.845 ± 0.164 g / cm2; Ward 0.563 ± 0.173 g / cm2 vs 0.657 ± 0.106 g / cm2; Trochanter: 0.666 ± 0.104 g / cm2 vs 0.725 ± 0.143 g / cm2; Whole Femur: 0.827 ± 0.182 g / cm2 vs 1.033 ± 0.161 g / cm2, both with p <0.001). To date (respectively, lumbar spine: 1.178 ± 0.761 g / cm2 Femoral neck: 0.989 ± 0.712 g / cm2; Ward 0.874 ± 0.982 g / cm2; Trochanter: 0.981 ± 0.382 g / cm2; Whole Femur: 1.036 ± 0.294 g / cm2). The TBS values ​​at the level of the lumbar spine were significantly lower in the prosthetic patients compared to the control group (respectively, 1.012 ± 0.163 score vs 1.361 ± 0.126 score, both with p <0.001). Average RSMIs are 5.42 ± 0.078kg / m² below the mean of the control population (5.7kg / m²) increased on average by 2.07 ± 0.078kg / m² compared to T0. Between the levels of TBS and the levels of RSMI respectively 1.914 ± 0.152 and 4.72 ± 0.029kg / m² there is a positive correlation with p <0.001; with an average implementation of TBS from T0 of 0.874 ± 0.121. A comparison of the 1-year data on the 55 concluded patients shows that the levels of TBS appear to be influenced by antiresorptive therapy; the improvement is more in the ALD group (60%) than in the DMAB group (40%); in both cases the improvement does not exceed 5-8% of total significance so it is not statistically detectable. The dosages of 25 (OH) D were found to be 13 ± 1.4 ng / ml at T0 and 24 ± 0.7 ng / ml at T1. The PTH values ​​were 40.36 ± 2.7 pg / ml at T0 and 47 ± 2.7 pg / ml at T1. Hb values ​​were 12.47 ± 1.1 g / L at T0 and 14.18 ± 0.97 g / L to T1. From the analysis of geriatric parameters respectively in the ALD vs DMAB group, we found: Hand-grip strength, Kg ± DS In female patients: 15.3 ± 5.3 vs 13.5 ± 6.2, in male patients 22.1 ± 5.0 vs 23.2 ± 1.6; Barthel Index, score ± SD 91 ± 14 vs 83 ± 23; ADL, n ° ± SD 5.5 ± 0.9 vs 5.1 ± 1.5; IADL, n ° ± SD 5.8 ± 2.5 vs 5.1 ± 3.4; MNA, score ± SD 11.4 ± 2.2 vs 10.4 ± 2.9 CIRS comorbidity, score ± SD 4.3 ± 1.8 vs 4.2 ± 1.6; CIRS severity, score ± SD 1.9 ± 0.5 vs 1.9 ± 0.3, SPMSQ, score ± SD 2.0 ± 2.2 vs 1.9 ± 2.1; BMI, mean ± SD 24.4 ± 5.2 vs 21.3 ± 2.9 Examining the basal characteristics from the bone and muscle point of view, first of all, a deficient state of Vitamin D common to the two groups is highlighted. In both, BMD is indicative of osteoporosis in the femoral neck and osteopenia in the spine (probably due to artifacts due to the presence of osteoarthritis and / or vertebral fractures). The TBS shows a slight difference between the two groups (DMab 1.129 ± 0.160 ALD 1.032 ± 0.162, p .073), indicating a condition of bone degradation in both. Considering the Hand Grip and RSMI values, with reference to the cut offs indicated in the EWGSOP2 Consensus, both groups show a state of “confirmed” sarcopenia. In particular, the values ​​of RSMI in women are frankly pathological, while those of men are at the lower limits (Ald 7.7 ± 1.2, Dmab 7.1 ± 0.1), but we must weigh the lower prevalence of males within the sample (12.2%). There is no real difference between the two drugs, even after adjustment for the variables (BMI and TBS). The percentage changes in RSMI clearly show a strengthening effect of the appendicular musculature from part of Denosumab, with statistically significant difference compared to Alendronate (Ald -5.8 ± 12.4 vs Dmab 0.5 ± 4.5, p = 0.046) Conclusions. Currently the study shows us how there is a correlation between the recovery of muscle mass, the reduction of fat mass and the functional, motor and fragility index recovery.This study shows that sarcopenia is common in elderly patients, mostly in those classified as normal or overweight according to BMI. Therefore, the TBS and BMD values ​​could play a key role in a muscle-bone feedback in the geriatric patient in the post-operative state such as that of the hip replacement. Patients who report fragility femur fractures are osteosarcopenic subjects, we must consider the syndrome, not the individual pathologies. linked to the transient immobilization following the event indicating that the continuation of therapy beyond the 1st year should be recommended and encouraged, in association with interventions aimed at favoring patient mobilization. Consistent with the resulting data, in association with an average increase in (OH) D, in the most compliant patients a more marked recovery is also observed on BMD, mirror of the bone mineral quantity, while the recovery on the quality of the bone shown by the analysis of trabecular bone (TBS) is lower. have a potential muscle strengthening effect, so it appears to be a promising approach to the elderly osteosarc patient openico. The TBS in association with the evaluation of the total metabolic body, prove additional clinical parameters compared to the standard densitometric values ​​on our sample of elderly patients, suggesting how these methods can improve the evaluation of "fragility" of the geriatric patient in the post-fracture period to improve 'diagnostic-therapeutic framework and better compliance with therapy. References .Rockwood K et al.Interdiscip Top Gerontol Geriatr. 2015;41:VII-X.;2.Chen KW et al.Worldviews Evid Based Nurs. 2017 Apr 27 3.Mitnitski AB et al. Biogerontology. 2017 Mar 2. ;4.Searle SD, Rockwood K. et al. Alzheimers Res Ther. 2015 Aug 3;7(1):54. 5.Strawbridge WJ et al.Med S ci 1998;53A:M9-16.;6.Chin A et al.J Clin Epidemiol 1999;52:1015-21.;7.Walston J et al. J Am Geriatr S oc 2006;54:991-1001.;8.Rantanen T et al.J Gerontol A Biol Med Sci 2000;55A:M168-73.;9.Rantanen T et al.J Am Geriatr S oc 2000;48:613-7.;10.Rozzini R et al.Arch I ntern Med 2001;161:299-300.;11.Brown JC et al.Aging Clin Exp Res. 2016 Mar 28 12.Villa P et al.J Endocrinol Invest. 2016 Feb;39(2):191-8..;13.Lamy O et al.Rev Med Suisse. 2011 Nov 2;7(315):2130, 2132-4, 2136.;14.Baumgartner RN et al., J Epidemiol. 147:755–76

Stratified medicine has tremendous potential to deliver more effective therapeutic intervention to improve public health. For practical implementation, reliable prediction models and clinically meaningful categorization of some comprehensible summary measures of individual treatment effect are vital elements to aid the decision-making process and bring stratified medicine to fruitful realization. We tackle the quantitative issues involved from three fronts : 1) prediction model building and selection; 2) reproducibility assessment; and 3) stratification. First, we propose a systematic model development strategy that integrates cross-validation and predictive accuracy measures in the prediction model building and selection process. Valid inference is made possible via internal holdout sample or external data evaluation to enhance generalizability of the selected prediction model. Second, we employ parametric or semi-parametric modeling to derive individual treatment effect scoring systems. We introduce a stratification algorithm with constrained optimization by utilizing dynamic programming and supervised-learning techniques to group patients into different actionable categories. We integrate the stratification and newly proposed prediction performance metric into the model development process. The methodologies are first presented in single treatment case, and then extended to two treatment cases. Finally, adapting the concept of uplift modeling, we provide a framework to identify the subgroup(s) with the most beneficial prospect; wasteful, harmful, and futile subgroups to save resources and reduce unnecessary exposure to treatment adverse effects. The proposals are illustrated by AIDS clinical study data and cardiology studies for non-censored and censored outcomes. The contribution of this dissertation is to provide an operational framework to bridge predictive modeling and decision making for more practical applications in stratified medicine.
Biostatistics

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Capes
Yersinina enterocolitica is a Gram-negative bacteria with zoonotic potential. It is associated with the occurrence of enteric diseases in humans. Pigs are considered the main source of Y. enterocolitica and the bacteria is mainly found in the pig’s palatine tonsils. The objective of this study was to evaluate the occurrence of pathogenic Y. enterocolitica in palatine tonsils of healthy pigs from Santa Catarina, during the slaughter process. In order to achieve this goal, a multiplex PCR technique was performed so as to detect the presence of virulence genes (ail, yadA and virF). This technique was compared to quantitative real time PCR (qPCR), only for the ail gene. Palatine tonsils were randomly collected from 400 pigs from four federally inspected slaughterhouses of the state of Santa Catarina. One positive sample was found for the three studied virulence genes, which were confirmed by DNA sequencing. The analysis of partial sequences of the three virulence genes identified three unique amino acid changes, one in the virF gene and two in YadA gene. This sample had 11.058.398 molecules/μL detected by qPCR. By comparing the two techniques, qPCR was 100 times more sensitive than standard PCR. This result shows low occurrence of pathogenic Y. enterocolitica in healthy pigs from federally inspected slaughterhouses in Santa Catarina
Yersinia enterocolitica é uma bactéria Gram-negativa emergente que possui potencial zoonótico e está associada a quadros de infecção alimentar em humanos. Os suínos são considerados o principal reservatório de Y. enterocolitica, abrigando-a principalmente nas tonsilas. Tendo em vista a carne suína como uma das mais consumidas no mundo e a importância deste agente zoonótico, o objetivo deste trabalho foi avaliar a ocorrência de Y. enterocolitica patogênica em tonsila de suínos no momento do abate no estado de Santa Catarina. Para isto, foi utilizada uma PCR convencional multiplex que detecta a presença de genes de virulência (ail, yadA e virF) e comparou-se esta técnica com a PCR quantitativa em tempo real (qPCR), somente para o gene ail. Foram coletadas aleatoriamente tonsilas de 400 suínos provenientes de quatro frigoríficos com inspeção federal em diferentes regiões do estado. Foi realizado o sequenciamento do DNA dos genes amplificados das amostras positivas na cPCR e posteriormente foi feita a análise filogenética. Apenas uma amostra foi positiva para os três genes pesquisados na PCR convencional, os quais foram confirmados por sequenciamento. A análise das sequências parciais dos três genes de virulência identificou três mudanças de aminoácidos exclusivas, sendo uma no gene virF e duas no gene yadA. Na qPCR esta amostra apresentou 11.058.398 moléculas/μL. Ao comparar as duas técnicas, a qPCR foi 100 vezes mais sensível que a PCR convencional. Isso demonstra uma baixa ocorrência de Y. enterocolitica patogênica em suínos sadios ao abate em frigoríficos com inspeção federal em Santa Catarina

Socialisation is a life long process in which people acquire the knowledge, rules, opinions and attitudes they need to adjust into a culture and a society. The cultural and traditional beliefs in a society influence gender roles in a society. Women in Zambia are subordinated men and suffer more from sexual and reproductive ill-health. Previous research show that females engage in more risk behaviors even though they have more positive attitudes towards safe sex which makes them more vulnerable when it comes to sexual and reproductive health. The aim of this study was to study the opinions about sex related information, and knowledge and attitudes about sexual and reproductive health among young girls. To get these answers a quantitative study was made in Kitwe in Zambia. The result showed that most of the respondents believe it to be important to get information about sex but almost half of them thought that they had got too little information. It also showed that the respondents believe themselves to have good knowledge about HIV/AIDS but a lower knowledge about contraceptives. To reduce the inequalities in health between women and men empowering women is of great importance.

Le scienze omiche sono attualmente in fase di sviluppo offrendo una nuova prospettiva dell'ambiente cellulare e dell'organismo. Tra queste, la genomica e la proteomica sono tra le più sviluppate. Al contrario, la lipidomica è ancora un campo emergente. L'importanza di fornire un forte approccio metodologico abbinato ad una rigorosa interpretazione dei dati è spiegata dalla recente scoperta del ruolo chiave dei lipidi come componenti strutturali e fonte energetica ma anche in molti processi biologici (secondi messaggeri, regolatori delle interazioni intercellulari e di carica superficiale, coinvolgimento in malattie metaboliche, cancro ecc.). La spettrometria di massa, grazie ai recenti e significativi progressi, è il metodo analitico più adatto in molte delle scienze omiche nonostante la loro integrazione sia ancora agli inizi e sia necessaria un'attenta ottimizzazione dei protocolli. Tuttavia, considerata la complessità molecolare, solo una visione multi-omica può darci un quadro completo dei processi intra- ed extra-cellulari in condizioni fisiologiche e patologiche nonché in risposta ad un'esposizione ambientale o chimica per contribuire infine al campo della medicina di precisione. Il progetto di ricerca qui presentato mira quindi a fornire prospettive di proteomica e lipidomica, sia come approccio singolo che integrato, a diverse domande di ricerca mediante spettrometria di massa ad alta risoluzione. L'indagine sul proteoma cutaneo di topi glabri mi ha permesso di mostrare come il peptide endogeno β-alanil-L-istidina (carnosina) agisca in difesa dei danni UV-A. Infatti, diversi importanti sistemi proteici hanno mostrato un'alterazione del trattamento con UV-A tra cui il pathway di segnale del calcio, la funzione mitocondriale o l'espressione della sirtuina, che sono stati tutti ripristinati da un trattamento preventivo della pelle mediante un'applicazione topica di carnosina. Queste alterazioni proteomiche potrebbero derivare (almeno in parte) da ROS generati da UV-A, o/e dalla generazione di prodotti di ossidazione lipidica (HNE, acroleina) derivanti dalla perossidazione di acidi grassi polinsaturi. L'implicazione di tali agenti è enfatizzata dalla potente efficacia del trattamento nel ripristinare un normale profilo proteomico delle pelli trattate con UV-A, in accordo con la sua capacità di neutralizzare la formazione di addotti sulle proteine e la loro successiva modificazione, ripristinando così la loro funzione. Passando alla lipidomica, l'importanza biologica recentemente dimostrata dagli esteri degli acidi grassi degli idrossiacidi grassi (FAHFA) ha richiesto l'ottimizzazione di un metodo su misura per la loro identificazione e quantificazione nella matrice umana. Infatti, crescenti evidenze sui ruoli fisiologici dei FAHFA, compresi quelli antinfiammatori, antidiabetici e immunomodulatori, motivano una più ampia caratterizzazione di questi lipidi come possibili biomarcatori e bersagli terapeutici per condizioni patologiche come il diabete o l'obesità. Tuttavia, la bassa concentrazione nei tessuti umani, la grande eterogeneità della struttura e il fatto che la maggior quantità di FAHFAs nelle cellule è incorporata nei trigliceridi sfidano gli attuali metodi analitici per la loro accurata identificazione e quantificazione. La preparazione dei campioni ottenuta e l'ottimizzazione del metodo strumentale hanno tuttavia permesso con successo di isolare, rilevare e quantificare per la prima volta FAHFA endogeni sul tessuto adiposo umano indicando alterazioni significative basate sullo stato metabolico (soggetti obesi insulino-sensibili o resistenti vs soggetti magri) e porzioni di tessuto adiposo (viscerale vs sottocutaneo). Questi risultati saranno utili per comprendere meglio le potenzialità biologiche di questi lipidi bioattivi nelle patologie metaboliche. Infine, i due studi multi-omici condotti in questo percorso di dottorato hanno avuto rispettivamente lo scopo di valutare gli effetti molecolari dell'acido ialuronico a basso peso molecolare (LMW-HA) nel proteoma e lipidoma di fibroblasti dermici umani e di analizzare i cambiamenti del profilo lipidomico e proteomico indotti dal trattamento di prevenzione con γ-Orizanolo in ratti obesi. LMW-HA ha mostrato un impatto sia sul profilo proteomico che lipidico, principalmente a una concentrazione pari allo 0.50%. I risultati di proteomica non solo sono stati confermati ma anche corroborati da quelli di lipidomica e dall’integrazione dei due approcci. Infatti, la funzionalità dei mitocondri, la maturazione delle cellule e il metabolismo dei lipidi si sono stati dimostrati in linea. Per quanto riguarda le modificazioni del lipidoma, abbiamo visto un particolare aumento di ceramidi, trigliceridi ed esteri del colesterolo, tutti coinvolti nell'idratazione della pelle e nel rinnovamento dell'epidermide sostenendo il ruolo benefico dell’ acido ialuronico a basso peso molecolare come ingrediente cosmetico. Tuttavia, il corretto equilibrio tra la loro sintesi e metabolismo è fondamentale per il benessere della pelle e ulteriori studi sono necessari per l’approfondimento di queste dinamiche. La valutazione degli effetti del γ-Orizanolo (Orz), invece, ha fornito solo uno scarso numero di alterazioni significative plasmatiche sia nel proteoma che nel lipidoma probabilmente a causa della debolezza del modello animale. Sono dunque necessari ulteriori studi per confermare la rilevanza biologica di Orz mostrata finora principalmente da test biologici. Per concludere, sebbene molte domande relative a questi temi di ricerca siano ancora senza risposta e altre omiche dovrebbero essere incluse in una visione integrativa (metabolomica ad esempio), durante questo percorso multidisciplinare di dottorato ho apprezzato la complessità e il valore dell’approccio omico nell'approfondire le nostre conoscenze in diversi campi di ricerca permettendo di avvicinarsi sempre più alla medicina di precisione, obiettivo finale di tutte le scienze omiche.
The ‘omics sciences are currently in development offering a new and combined perspective of cellular and organismal environment. Among these, genomics and proteomics are among the most developed while lipidomics is still an emergent field. The importance to provide a strong methodological approach paired to a rigorous data interpretation is explained by the recent discovery of the lipids’ key role not only as structural components and energetic source but also in many biological processes (i.e., second messengers, regulators of inter-cellular interactions and of surface charge, involvement in metabolic diseases, cancer etc.). Thanks to the recent significant advances, mass spectrometry is the most suitable analytical method in many of ‘omics sciences despite their integration is still at the beginning and a careful optimization of protocols is needed. Nevertheless, considering the molecular complexity, only a multi-omics vision can give a complete picture of intra- and extra-cellular processes in physiological and pathological conditions as well as in response to an environmental or chemical exposure to finally contribute to the field of precision medicine. So, the work herein aims to provide proteomics and lipidomics perspectives, both as single and integrated approaches, to different research questions by high-resolution mass spectrometry. At first, the investigation on skin hairless mice proteome allowed me to show how an endogenous peptide, β-alanil-L-histidine (a.k.a. carnosine), is acting in defense of UV-A damages. Indeed, several major protein systems shown an alteration by UV-A treatment including calcium signaling, mitochondrial function or sirtuin expression, which were all restored by a preventive treatment of the skins by a topical application of carnosine. These proteomics alterations could result (at least in part) from ROS generated by UV-A, or/and the generation of lipid oxidation products (HNE, acrolein) resulting from the peroxidation of polyunsaturated fatty acids in the irradiated skins. The implication of such agents is emphasized by the potent efficacy of carnosine in restoring a normal proteomic profile of UV-A-treated skins, in accordance with its ability to neutralize the formation of adducts on proteins and their subsequent modification, thereby restoring their function. Moving to lipidomics, the biological importance recently demonstrated by fatty acid esters of hydroxy fatty acids (FAHFAs) asked for a tailored method optimization for their identification and quantification in human matrix. In fact, increasing evidence on the physiological roles of FAHFAs, including anti-inflammatory, anti-diabetic and immunomodulatory ones, motivates a more extensive characterization of these lipids as possible biomarkers and therapeutic targets for pathological conditions such as diabetes or obesity. Nevertheless, the low concentration in human tissues, the large structure heterogeneity and that the major amount of FAHFAs in cells is incorporated into triacylglycerols challenge current analytical methods for their accurate identification and quantification. The achieved samples’ preparation and instrumental method optimization successfully enabled to isolate, detect, and quantify endogenous FAHFAs for the first time on human adipose tissue revealing significant alterations based on metabolic status (obese insulin sensitive or resistant vs lean subjects) and adipose tissue portions (visceral vs subcutaneous). These results will be useful to better understand the biological potentiality of this bioactive lipids in metabolic pathologies. Then, the two multi-omics studies herein conducted were aimed to evaluate molecular effects of low-molecular-weight hyaluronic acid (LMW-HA) in proteome and lipidome of normal human dermal fibroblasts and to analyze lipidome and proteome profile changes induced by γ-Oryzanol (Orz) prevention treatment in obese-induced rats, respectively. LMW-HA showed an impact both on proteome and lipidome profile, mainly at 0.50 % of concentration. The proteomics results were not only confirmed but also corroborated by lipidomics and integratomics ones. Indeed, mitochondria functionality, cells maturation and lipids metabolism were concordantly demonstrated. About lipidome changes, we saw a particular increasing of ceramides, triacylglycerols and cholesterol esters involved in the skin moisturizing and epidermis renewal and so supporting the beneficial role of low-molecular weight as cosmetic ingredient. Nevertheless, the correct balance between their synthesis and degradation is essential for the skin wellness and further studies are necessary for the deepening of these dynamics. The Orz’s effects assessment, instead, provided only marginal significant alterations both in plasma’s proteome and lipidome probably due to the weakness of the animal model. Further thoughts and experiments are needed to confirm the biological relevance of Orz mainly showed in biological tests so far. To conclude, although a lot of questions related to these research topics are still unanswered and other omics should be included in an integrative vision (metabolomics for example), during this multidisciplinary PhD journey I appreciated the complexity and the value of omics sciences in deepening our knowledge about several research fields approaching more and more the precision medicine goal.

Thesis submitted in fulfilment of the requirements for the degree Master of Technology: Horticulture in the Faculty of Applied Sciences at the Cape Peninsula University of Technology
The high demand for medicinal plants has favoured over-exploitation of wild plants. The search for alternative and sustainable methods of medicinal plant cultivation is imperative and desirable. Biotechnological approaches particularly hydroponic technology has the potential for large scale plant cultivation and production of secondary metabolites. The current study aims at optimizing the production of antimicrobial secondary metabolites by an indigenous South African medicinal plant species (Helichrysum cymosum) through hydroponics N and K fertilization. In Chapter 1, the conceptual framework and justifications of the study are presented. In Chapter 2 the research objective was to discern the optimal potassium (K) supplement level for H. cymosum by evaluating the effects of different hydroponic K levels on growth, K-leaf content, and anti-Fusarium oxysporum f.sp.glycines (Ascomycota: Hypocreales) and total activities. Six weeks old seedlings of H. cymosum were treated with varied concentrations of K in the form of potassium chloride, potassium nitrate and monopotassium phosphate (58.75, 117.5, 235 and 470 ppm). These concentrations were based on a modification of Hoagland’s hydroponic nutrient formula. Plants were maintained under greenhouse conditions and growth parameters (plant height and number of leaves) were recorded weekly. At 8 weeks post treatment, plants were harvested and fresh weights were recorded and tissue nutrient content analysed. Sub-samples of the aerial parts of plants grown in the different treatments were air dried, extracted with acetone and tested against F. oxysporum. Plants exposed to 235 ppm K showed a marked increase in leaf number, plant height and fresh weight. Overall there was no significant difference (P > 0.05) among the treatments with respect to tissue nutrient content; K ranged from 3.56 ± 0.198 to 4.67 ± 0.29 %. The acetone extraction yield increased with increasing K fertilization: 58.75 ppm (16.67 ± 2.35 mg), 117.5 ppm (22.5 ± 4.79 mg), 235 ppm (210 ± 38.5 mg) but dropped to 40 ± 4.08 mg at 470 ppm K. Results from the anti-F. oxysporum bioassay showed that 58.75 and 235 ppm K treatments produced the most bioactive acetone extracts; MIC values of 0.49 and 0.645 mg/l, respectively. Acetone extracts obtained from plants exposed to 235 ppm K yielded the highest total activity, comparatively (P < 0.05). In conclusion, the optimum nutrient K level for growing H. cymosum hydroponically was 235 ppm. Chapter 3 focused on another important macro nutrient N and the objective was to determine the optimum nutrient requirements for growing the medicinal plant, Helichrysum cymosum (L.) (Asteraceae), hydroponically. Experiments were conducted to assess the effects of varied nitrogen (N) concentrations supplied as nitrate and ammonium on growth, tissue nutrient content, antimicrobial and total activities of acetone extracts of aerial parts. Treatments were based on a modified Hoagland’s nutrient formula. Six week old rooted cuttings were treated with 52.5 ppm, 105 ppm, 210 ppm and 420 ppm of N. Leaf number and stem height (cm) were recorded at weekly intervals and leaf analysis conducted. The effects of N treatments on plant growth parameters varied significantly among treatments; 52.5 ppm of N yielded the tallest plants (height) [19.4 ± 0.7 cm], while 105 ppm N yielded the maximum leaf number (68.1 ± 6.2) as well as maximum fresh weight of aerial parts was obtained with 105 ppm (15.12 ± 1.68 g). Nitrogen content of plant tissue ranged between 0.53 ± 0.03 and 4.74 ± 0.29% (d, f, 3, 12; f=14; P ≤ 0.002) depending on treatments. Powdered aerial parts (5 g) of H. cymosum obtained from the different N treatments were extracted with 100 ml of acetone. N treatment significantly affected the yield of crude extracts, which ranged from 87.5 ± 15.5 (52.5 ppm) to 230 ± 23.5 mg (105 ppm). Acetone extracts of plants that were exposed to varied N treatments were screened for anti-Fusarium oxysporum activity using minimum inhibitory concentration (MIC) method. The MIC value (0.073 ± 0.014 mg/ml) obtained with acetone extracts of plants exposed to 52.5 ppm N was significantly lower compared to the MICs of the other N treatments (105 [0.47 ± 0 and 0.705 ± 0.135 mg/ml], 210 [0.234 and 0.47 mg/ml] and 420 ppm [0.29 ± 0.101 mg/ml]) at 24 and 48 hours respectively. However, the total activities of extracts obtained among the four N treatments, which ranged from 0.062 ± 0.02 to 0.26 ± 0.06 ml/g was not statistically different at 24 or 48 hours (P > 0.05). LC-MS analysis of acetone extracts of H. cymosum plants obtained from the four treatments hinted that known anti-microbial agents such as apigenin, quercetin, kaempferol, helihumulone and quinic acids were present in the extracts and the quantity of helihumulone increased with increased nutrient N level. These results suggest that H. cymosum may be cultivated hydroponically and that the antimicrobial activity and/or the phytochemical profile of the crude acetone extracts is affected by nutrient nitrogen levels. Hydroponic cultivation of plants may be able to alleviate to an extent the pressure on wild medicinal plants.

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Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq
INTRODUCTION: When discussing the living transplant donation, the focus is, most of the times, in the organ?s receptor. After all, he is the sick ne, the patient, the reason of the process development that culminates in the surgery for function substitution. However, the donor is a complicated and fundamental part on the procedure, so that in the contrary of the other part, is an healthy subject that becomes a patient. Accepts mutilation, after emphatic identification with the one whose life quality is modified by a dysfunction. Various researchers have been studying the psychological, social and ethical implications involving kidney donors (BURROUGHS et al., 2003; STERNER et al., 2006; NEUHAUS et al., 2005). The donor subject that offers a body part for transplant will be bequeathing an invaluable gift and who receives the organ accepts it. To give and receive a present of that value may be the most important in this story filled with meanings of the human organ transplant. This extraordinary present, on the other hand, is not and private transaction between donor and receptor. On the contrary, happens inside a complex personal relationship network, wich is extended to families, doctors and all the other members of the health team that are involved in the operation. Inside the relationship network, a complex exchange happens, in which considerably more than an organ is transferred. (FOX & SWAZEY, 1978). OBJECTIVES: To know the donor subject profile and hos perception after the kidney donation in kidney transplantation. METHODOLOGY: The study proposed was observational, explanatory and transverse. The data were analyzed both in qualitative and quantitative ways. The subjects were called to enter the study, submmited toclinical and psychological evaluation (application of SF-36, Beck?s Depression Scale, and structured interview). The studied sample consisted of 47 individuals. The average pos-donation time of the evaluated subjects was 4 [1 ? 8] min 0 29 max. RESULTS: The main relationship between donor and receptor was maternal, being the characteristics in that case: woman, about 45 years old, overweighed, consanguineous to the receptor, with incomplete fundamental scholarship, living with companion and children. Clinically, after tga donation, the donors presented, mostly, overweight (IMC 27,6), blood pressure between the normal limits (123 ? 18,1/78,5 ? 10 mmHg), protein?ria in urine sample of 6 mg [5 mg; 8 mg], 131,55? 70,58 of creatinina in urine sample and 1,28 (1,28? 0,27) of creatinina s?rica. The transplant surgery was 74,5% realized by Videolaparoscopia and 25,5% by open surgery. The quality of life, evaluated by the SF 36, presented a variation of 59,2 ? 24,9 (Vitality) to 79,4 ? 24,3 (Functional Capability). The depression can be classified in the following way: 33 (70,21%) with minimal depression, 6 (12,70%) with low depression, 5 (10,63%) with moderated depression and 3 (6,30%) with severe depression. About the parental factor, 11 donors were not-related and 36 were related. In their majority, 41 (87,3%) the donors keep contact with the receptors, 28 (59,6%) referred that the relationship has not changed after the donation, 24 (51,1%) referred that had some kind of emotional limitation, 11 (23,4%) referred that the pain they felt was the most negative factor of the donation, 40 (85,1%) said that seeing the receptor well was the most positive aspect, 5 (10,6%) felt pressure to donate, 4 (8,5%) regretted on donating. CONCLUSION: It is concluded that it was possible to know the donors profile and their perception after the kidney donation and kidney transplantation.
INTRODU??O: Quando se discute a doa??o inter vivos em transplante, o foco da aten??o na maior parte das vezes ? o receptor de ?rg?o. Afinal, ele ? o doente, o paciente, o motivo do desenvolvimento do processo que culmina em cirurgia para substitui??o de fun??o. No entanto, o doador ? parte implicada e fundamental no procedimento, tanto que ao contr?rio do outro, ? um sujeito h?gido que torna-se paciente. Aceita mutila??o, ap?s identifica??o emp?tica com aquele cuja qualidade de vida encontra-se modificada por uma disfun??o O sujeito doador que oferece uma parte de seu corpo para transplante est? legando um inestim?vel presente e quem recebe o ?rg?o aceita o presente sem pre?o. Dar e receber um presente com este valor talvez seja o mais importante nesta hist?ria recheada de significados do transplante de ?rg?os humanos. Este extraordin?rio presente, por outro lado, n?o ? uma transa??o privada entre o doador e o receptor. Pelo contr?rio, ocorre dentro de uma complexa rede de relacionamentos pessoais que se estende para fam?lias, m?dicos e todos os membros da equipe de sa?de que est?o envolvidos na opera??o. Dentro desta rede de rela??es, uma complexa troca ocorre, pela qual,consideravelmente, mais do que o ?rg?o ? transferido. (FOX & SWAZEY, 1978). OBJETIVOS: Conhecer o perfil do sujeito doador e sua percep??o ap?s a doa??o de rim em transplante renal. METODOLOGIA: O estudo proposto foi observacional,explorat?rio e transversal. Os dados analisados de forma qualitativa e quantitativa. Os sujeitos foram convocados a participar do estudo, avaliados clinica e psicologicamente (aplica??o dos instrumentos SF-36 e Escala de Depress?o de Beck, al?m de estruturada). A amostra estudada foi composta por 47 indiv?duos. O tempo m?dio p?s-doa??o dos sujeitos avaliados foi de 4 anos. RESULTADOS: A principal rela??o entre o doador e o receptor foi materna, sendo neste caso as caracter?sticas: mulher, ao redor dos 45 anos, com sobrepeso, consang??nea com o receptor, com escolaridade de ensino fundamental incompleto, vivendo com companheiro e filhos. Clinicamente, ap?s a doa??o, os doadores apresentaram, em sua maioria, sobrepeso (IMC 27,6), press?o arterial dentro dos limites da normalidade (123 ? 18,1/78,5 ? 10 mmHg) e fun??o renal normal (creatinina s?rica m?dia de 1,28 mg/dl e aus?ncia de protein?ria [protein?ria em amostra urin?ria de 0,0456 mg/g de creatinina]). A cirurgia de transplante foi realizada por v?deolaparoscopia em 74,5% e por cirurgia aberta 25,5% . A qualidade de vida, avaliada atrav?s do SF 36, apresentou uma varia??o entre 59,2 ? 24,9 (Vitalidade) at? 79,4 ? 24,3 (Capacidade funcional). A depress?o pode ser classificada da seguinte maneira: 33 (70,21%) com depress?o m?nima, seis (12,70%) com depress?o leve, 5 (10,63%) com depress?o moderada, e 3 (6,30%) com depress?o grave. Quanto ao fator parentesco, 11 doadores eram n?o-parentes e 36 eram parentes. Em sua maioria,(87,3%), os doadores mant?m contato com os receptores, 28(59,6%) referem que o relacionamento n?o mudou ap?s a doa??o, 24( 51,1%) referem que tiveram alguma limita??o emocional, 11(23,4%) referiram que a dor que sentiram foi o aspecto mais negativo da doa??o, 40(85,1%) disseram que ver o receptor bem foi o aspecto mais positivo, 5(10,6%) se sentiram pressionados para doar e 4( 8,5%) se arrependeram de doar. CONCLUS?O: Conclui-se que foi poss?vel conhecer o perfil dos doadores e sua percep??o ap?s a doa??o de rim em transplante renal.

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Study the medical education process is part of a worldwide movement of health review, motivating important initiatives, represented in Brazil by the national curriculum guidelines of the courses in this area, presented by the Ministry of Education in 2001. In order to compare the effects of content learning/retention (outcome) of dialogued lecture (factor under study), we carried out a randomized controlled trial by groups, blinded to the research subjects with medical students from the 7th and 8 th semester from a private university in southern Brazil, with grade five assigned by the Higher Education Personal Improvement Commission (CAPES). 150 subjects were evaluated between March 2012 and June 2014, average age 24. 7 years and a predominance of females (62. 7%); 69 (46%) allocated for dialogued lecture (intervention group) and 81 (54%) to traditional lecture (control group). The performance of groups was evaluated by the same theoretical knowledge test administered before and after class, where students in the control group showed greater variation between the first and second test (8. 6 vs. 6. 7 p = 0. 0001) result reinforced by the magnitude of the effect also higher in this group (2,526 vs. 1,350). In the pretest, without distinction by group, the overall student achievement was 50%, with a higher average score of the intervention group (p = 0. 003) and those students tested in the 7th semester. In this study, the expository dialogue-class determined final results similar to traditional classroom (20. 2 vs. 20. 0 points in the final test) no impairment in short-term learning was noticed.
Estudar o processo de educação médica é parte de um movimento mundial de revisão da saúde, motivando iniciativas importantes, representadas no Brasil pelas diretrizes curriculares nacionais dos cursos desta área, apresentadas pelo Ministério da Educação no ano de 2001. Com o objetivo de comparar os efeitos de aprendizagem/retenção de conteúdo (desfecho) da aula expositiva dialogada (fator em estudo), realizou-se um estudo controlado randomizado por grupos, cegado para os sujeitos de pesquisa com alunos do 7º e 8º semestre do curso de medicina de uma Faculdade privada do sul do Brasil, com conceito cinco atribuído pela Comissão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Foram avaliados 150 sujeitos, entre março de 2012 e junho de 2014, média de idade de 24,7 anos e predomínio do sexo feminino (62,7%); 69 (46%) alocados para a aula expositiva dialogada (grupo intervenção) e 81 (54%) para aula expositiva tradicional (grupo controle). O desempenho dos grupos foi avaliado por um mesmo teste teórico de conhecimento aplicado antes e após a aula, onde os alunos do grupo controle demonstraram maior variação entre o primeiro e segundo teste (8,6 vs. 6,7 p=0,0001) resultado reforçado pela magnitude do efeito também maior neste grupo (2,526 vs. 1,350). No pré-teste, sem distinção por grupo, o aproveitamento geral dos alunos foi de 50%, sendo maior a pontuação média do grupo submetido à intervenção (p=0,003) e daqueles alunos testados no 7º semestre. Neste estudo, a aula expositiva dialogada determinou resultados finais similares à aula tradicional (20,2 vs. 20,0 pontos no teste final) não sendo observado prejuízo na aprendizagem de curto prazo.

Children’s lifestyle has changed significantly during the recent decades, with an increasing prevalence of obesity as one outcome. Parents are usually the most influential people in young children’s lives. The overall aim of this thesis was to investigate parental perspectives on factors associated with 3-6 year-old children’s lifestyle, regarding eating habits and physical activity. Another objective was to compare different approaches to conducting postal questionnaires in terms of response rate, time consumption and cost-efficiency. The samples in the four studies were parents of 6-year-olds (n=158), parents of 3-year-olds (n=873), parents of 4-year-olds (n=30) and parents of 3-year-olds (n=353). In the first study, a questionnaire regarding practices and attitudes towards their child’s lifestyle, perceived obstacles and desired support was used. The second study included the Swedish Parenthood Stress Questionnaire (SPSQ), the Relationship Questionnaire (RQ) and the CFQ (Child Feeding Questionnaire). Parents also reported their child’s TV-viewing habits. The child’s measured height, weight and BMI were obtained from a register, BASTA. In the third study, focus group interviews were performed. The fourth study investigated three types of consent given for participation in a survey. The results showed that parents’ attitudes towards children’s lifestyle, in general, were “healthier” than their reports of their child’s daily practices. The practices differed depending on the parents’ educational background. Significant and dose-dependant associations were found between perceived maternal stress and children’s overweight, but also underweight. Parents felt that they were mainly responsible for their preschool child’s lifestyle. However, parents described challenges that limited and obstructed them from providing their child with a healthy lifestyle, citing the need to receive professional and peer support, while also requesting support from society. Allowing respondents to actively decline participation yielded a higher response rate and proved to be the most cost-efficient method for conducting a postal questionnaire.

The studies presented here evaluate the biliary, parenchymal and vascular enhancement effects of two T1-shortening liver-specific contrast agents, Gd-BOPTA and Gd-EOB-DTPA, in Magnetic Resonance Imaging (MRI) of healthy subjects and of patients. Ten healthy volunteers were examined with both contrast agents in a 1.5 T MRI system using three-dimensional gradient echo sequences for dynamic imaging until five hours after injection. The enhancement of the common hepatic duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma. While Gd-EOB-DTPA gave an earlier and more prolonged enhancement and image contrast of the bile duct, Gd-BOPTA achieved higher maximal enhancement and higher image contrast for all vessels studied during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma. In a third study, another 10 healthy volunteers were examined with the same protocol in another 1.5 T MRI system. Using signal normalization and a more quantitative, pharmacokinetic analysis, the hepatocyte-specific uptake of Gd-EOB-DTPA and Gd-BOPTA was calculated. A significant between-subjects correlation of the uptake estimates was found and the ratio of these uptake rates was of the same magnitude as has been reported in pre-clinical studies. The procedure also enabled quantitative analysis of vascular enhancement properties of these agents. Gd-BOPTA was found to give higher vessel-to-liver contrast than Gd-EOB-DTPA when recommended doses were given. In the final study, retrospectively gathered datasets from patients with hepatobiliary disease were analyzed using the quantitative estimation of hepatic uptake of Gd-EOB-DTPA described in the third study. The uptake rate estimate provided significant predictive ability in separating normal from disturbed hepatobiliary function, which is promising for future evaluations of regional and global liver disease. In conclusion, the differing dynamic enhancement profiles of the liver-specific contrast agents presented here can be beneficial in one context and challenging in another. Diseases of the liver and biliary system may affect the vasculature, parenchyma or biliary excretion, or a combination of these. The clinical context in terms of the relative importance of vascular, hepatic parenchymal and biliary processes should therefore determine the contrast agent for each patient and examination. A quantitative approach to analysis of contrast-enhanced liver MRI examinations is feasible and may prove valuable for their interpretation.

This survey is to study the attitudes, personal experiences of Health care professional students, and knowledge about the basic concepts of Traditional Chinese Medicine (TCM) in Hong Kong and Guangzhou district of Mainland China. The research methodology used was a questionnaire which was distributed amongst healthcare professional students in Hong Kong and Guangzhou. About Seventy-five percent of participants have ever used TCM at some time to treat minor diseases. On a scale from zero to ten, the mean (SD) scores for the perceived effectiveness of TCM were 6.55 (2.07), and most of them (89%) gave five to nine scores. The average proportion of TCM used in their whole lives estimate was 24%. Most of participants (83.3%) used TCM only one to five times per year in the last five years. In participants’ opinion, TCM is more natural and having less adverse effect, while WM is pure, specific, credible, easy to administer and having better patients’ compliance. WM was the priority, or even first choice when the participants faced with a variety of representative diseases. And people had a good understanding degree of some basic concepts of TCM. Although there were a few differences in gender groups comparing and district groups comparing, broadly speaking the similarities still were in majority. In conclusion, most of pharmacy students have their own knowledge about TCM, but more measures must be carried out to improve the popularizing rate of TCM. Moreover, mainland students have better knowledge of TCM and more positive attitude compared to TCM. The attitude and practice do not appear to vary significantly between genders.
published_or_final_version
Pharmacology and Pharmacy
Master
Master of Medical Sciences

An important goal of single photon emission tomography (SPECT) is the determination of absolute regional radionuclide concentration as a function of time. Quantitative and qualitative studies of SPECT with regard to clinical application is the object of this work. Three basic approaches for image reconstruction and factors which affect the choice of a reconstruction algorithm have been reviewed, discussed and the reconstruction techniques, GRADY and CBP evaluated, based on computer modelling. A sophisticated package of computational subroutines, RECLBL, for image reconstruction and for generation of phantoms, which was fully implemented on PRIME was used throughout this study. Two different systems, a rotating gamma-camera and a prototype scanning-rig have been used to carry out tomography experiments with different phantoms in emission and transmission mode. Performance assessment and reproducibility of the gamma-camera was tested prior to the experimental work. SPECT studies are generally hampered for a number of reasons, the most severe being attenuation and scattering. The effect of scattered photons on image quality was discussed, three distinct techniques were utilised to correct the images and results were compared. Determination of the depth of the source, Am-241 and Tc-99m in the attenuating media, water and TEMEX by analysing the spectroscopic data base on the SPR and spatial resolution was studied, results revealed that both techniques had the same range of depth sensitivity. A method of simultaneous emission and transmission tomography was developed to correct the images for attenuation. The reproducibility of the technique was examined. Results showed that the technique is able to present a promising and a practical approach to more accurate quantitative SPECT imaging. A procedure to evaluate images, under certain conditions has been defined, its properties were evaluated using computer modelling as well as real data. Usefulness of the odd sampling technique to improve image quality has been investigated and is recommended.

Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s. Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate. In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above. Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented. The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations. When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe. The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Study the medical education process is part of a worldwide movement of health review, motivating important initiatives, represented in Brazil by the national curriculum guidelines of the courses in this area, presented by the Ministry of Education in 2001. In order to compare the effects of content learning/retention (outcome) of dialogued lecture (factor under study), we carried out a randomized controlled trial by groups, blinded to the research subjects with medical students from the 7th and 8 th semester from a private university in southern Brazil, with grade five assigned by the Higher Education Personal Improvement Commission (CAPES). 150 subjects were evaluated between March 2012 and June 2014, average age 24.7 years and a predominance of females (62.7%); 69 (46%) allocated for dialogued lecture (intervention group) and 81 (54%) to traditional lecture (control group). The performance of groups was evaluated by the same theoretical knowledge test administered before and after class, where students in the control group showed greater variation between the first and second test (8.6 vs. 6.7 p = 0.0001) result reinforced by the magnitude of the effect also higher in this group (2,526 vs. 1,350). In the pretest, without distinction by group, the overall student achievement was 50%, with a higher average score of the intervention group (p = 0.003) and those students tested in the 7th semester. In this study, the expository dialogue-class determined final results similar to traditional classroom (20.2 vs. 20.0 points in the final test) no impairment in short-term learning was noticed.
Estudar o processo de educa??o m?dica ? parte de um movimento mundial de revis?o da sa?de, motivando iniciativas importantes, representadas no Brasil pelas diretrizes curriculares nacionais dos cursos desta ?rea, apresentadas pelo Minist?rio da Educa??o no ano de 2001. Com o objetivo de comparar os efeitos de aprendizagem/reten??o de conte?do (desfecho) da aula expositiva dialogada (fator em estudo), realizou-se um estudo controlado randomizado por grupos, cegado para os sujeitos de pesquisa com alunos do 7? e 8? semestre do curso de medicina de uma Faculdade privada do sul do Brasil, com conceito cinco atribu?do pela Comiss?o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES). Foram avaliados 150 sujeitos, entre mar?o de 2012 e junho de 2014, m?dia de idade de 24,7 anos e predom?nio do sexo feminino (62,7%); 69 (46%) alocados para a aula expositiva dialogada (grupo interven??o) e 81 (54%) para aula expositiva tradicional (grupo controle). O desempenho dos grupos foi avaliado por um mesmo teste te?rico de conhecimento aplicado antes e ap?s a aula, onde os alunos do grupo controle demonstraram maior varia??o entre o primeiro e segundo teste (8,6 vs. 6,7 p=0,0001) resultado refor?ado pela magnitude do efeito tamb?m maior neste grupo (2,526 vs. 1,350). No pr?-teste, sem distin??o por grupo, o aproveitamento geral dos alunos foi de 50%, sendo maior a pontua??o m?dia do grupo submetido ? interven??o (p=0,003) e daqueles alunos testados no 7? semestre. Neste estudo, a aula expositiva dialogada determinou resultados finais similares ? aula tradicional (20,2 vs. 20,0 pontos no teste final) n?o sendo observado preju?zo na aprendizagem de curto prazo.

The advents of technologies have led to tremendous increases in the diversity and size of the available data. In the field of medicine, the advancements in medical imaging technologies have dramatically improved the quality of the acquired data, such as a higher resolution and higher signal-to-noise ratio. In addition, the dramatic reduction of the acquisition time has enabled the studies of organs under function.At the same pace, the progresses in the field of biology and bioinformatics have led to stable automatic algorithms for the generation of biological data. As the amount of the available data and the complexity increase, there have been great demands on efficient analysis and visualization techniques to support quantitative visual analysis of the huge amount of data that we are facing. This thesis aims at supporting quantitative visual analysis in the presence of data uncertainty within the context of medicine and biology. In this thesis, we present several novel analysis techniques and visual representations to achieve these goals. The results presented in this thesis cover a wide range of applications, which reflects the interdisciplinary nature of scientific visualization, as visualization is not for the sake of visualization. The advances in visualization enable the advances in other fields. In typical clinical applications or research scenarios, it is common to have data from different modalities. By combining the information from these data sources, we can achieve better quantitative analysis as well as visualization. Nevertheless, there are many challenges involved along the process such as the co-registration, differences in resolution, and signal-to-noise ratio. We propose a novel approach that uses light as an information transporter to address the challenges involved when dealing with multimodal data. When dealing with dynamic data, it is essential to identify features of interest across the time steps to support quantitative analyses. However, this is a time-consuming process and is prone to inconsistencies and errors. To address this issue, we propose a novel technique that enables an automatic tracking of identified features of interest across time steps in dynamic datasets. Although technological advances improve the accuracy of the acquired data, there are other sources of uncertainty that need to be taken into account. In this thesis, we propose a novel approach to fuse the derived uncertainty from different sophisticated algorithms in order to achieve a new set of outputs with a lower level of uncertainty. In addition, we also propose a novel visual representation that not only supports comparative visualization, but also conveys the uncertainty in the parameters of a complex system. Over past years, we have witnessed the rapid growth of available data in the field of biology. The sequence alignments of the top 20 protein domains and families have a large number of sequences, ranging from more than 70,000 to approximately 400,000 sequences. Consequently, it is difficult to convey features using the traditional representation. In this thesis, we propose a novel representation that facilitates the identification of gross trend patterns and variations in large-scale sequence alignment data.

The ISBN 978-91-7519-514-8 on the title page is incorrect. The correct ISBN is 978-91-7519-415-8.

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Na última década vários modelos para análises quantitativas de dados etnobotânicos e etnofarmacológicos têm sido propostos e são, em sua maioria, baseados no consenso dos informantes. Neste trabalho nós procuramos testar a eficiência de diferentes estratégias metodológicas, comparando um índice (Valor de Importância Sindrômica - VIS) com os critérios de priorização baseado na lista livre e duas formas aleatórias para escolha de plantas dentro da abordagem etnodirigida. Essa eficiência foi avaliada por meio dos teores de taninos e flavonóides, associado com plantas que sugerem atividade cicatrizante e antiinflamatória. Para isso, realizamos entrevistas em uma comunidade rural na Caatinga do Nordeste do Brasil. Verificamos que o VIS demonstrou ser uma ferramenta eficaz ao revelar plantas com altos teores de taninos. Observamos que na comunidade estudada, os teores de flavonóides não estão relacionados com plantas indicadas no tratamento de inflamações e como cicatrizantes. Concluímos, entre outras coisas, que plantas medicinais da Caatinga conhecidas e/ou usadas para atividade antiinflamatória e cicatrizante são um bom critério para encontrar espécies com altos teores de taninos, porém este mesmo critério não serve para revelar plantas com altos teores de flavonóides

Reverse transcriptase (RT) is a crucial enzyme for retrovirus replication, and its presence in the virion is indispensable for infectivity. This thesis illustrates the use of RT activity assays as tools for quantitation and characterization of different retroviruses, particularly HIV.

A non radioactive assay, using microtiter plates, for the RT of Moloney murine leukemia virus (MMuLV) was developed. Assay conditions for MMuLV and HIV-1 RT, together with isozyme specific RT activity blocking antibodies, were shown useful for discrimination between RTs from different retrovirus genera. RT activity assay for HIV-1 was found to quantitate different subtypes more equally efficient than p24 antigen assays did.

Viral load (VL), the amount of HIV particles in the blood, is an important marker of the clinical status of an infected person. A method for VL determination based on RT activity (ExaVir Load) was developed. After plasma pretreatment, to inactivate cellular DNA polymerases, virions in patient plasma were immobilized on a gel, which was washed to remove disturbing factors. The virions were lysed with a detergent containing buffer and the lysate eluted. Finally, the RT activity in the lysate was determined and found to correlate strongly to VL by RNA according to a PCR based standard method (Roche Amplicor 1.5). The second version of the method was able to measure VL down to approximately 400 HIV-1 RNA copies/ml. The usefulness of RT from the VL procedure for determination of susceptibility towards anti-HIV drugs was demonstrated, and the results were in agreement with genotypic data.

Due to its technical simplicity, and ability to detect a broad range of HIV-1 subtypes, ExaVir Load and the drug susceptibility application are interesting for clinical use, particularly but not only in resource limited settings. The concept is also potentially useful for research purposes, e.g. in combination with specific RT assay conditions.

This thesis investigates the relationship between quantitative correlates of diffuse brain damage and neurological and psychiatric manifestations in Systemic Lupus Erythematosus (SLE). A group of 37 patients with a primary diagnosis of SLE (mean age 43.97±12.SS) were compared to 29 matched healthy controls. The SLE group were subdivided into those who had experienced neuropsychiatric (NP) manifestations (NPSLE - n=lS) and those who had never had NP manifestations (non-NPSLE). Participants completed a broad cognitive test battery, neuropsychological measures and quantitative MRI (magnetisation transfer (MTI) and diffusion tensor imaging (OTI)). From MTI the magnetisation transfer ratio (MTR) was measured, which can be a marker for demyelination. Using OTI the extent (apparent diffusion coefficient) and directionality (fractional anisotropy) of diffusion were assessed, which are sensitive measures of brain structural integrity. Results indicate that both SLE groups had significantly higher scores on depression and anxiety and lower quality of life compared to healthy controls. The only difference between the NPSLE and non-NPSLE groups was lower physical health related quality of life in the former group. On cognitive tasks the NPSLE group scored significantly worse than controls on multiple domains, and worse than the non-NPSLE group on memory and speed of processing. There were no differences between the non-NPSLE patients and controls. On OTI measures the NPSLE group showed increased white matter ADC and a non significant decrease in FA, changes which are consistent with subtle brain damage in this group. The non-NPSLE group had higher ADC than controls if measured in the whole brain. There were no differences on MTI and few differences on measures of brain volume, suggesting demyelination and atrophy were not noteworthy in this cohort. Correlations were assessed between cognition and the other factors. In the NPSLE group cognitive function correlated with white matter FA suggesting this was driven by changes in brain parenchyma. Cognitive function also correlated with pain, fatigue, physical health, disease activity and anxiety scores suggesting general health related factors also play a role in cognitive dysfunction. In the non-NPSLE group processing speed correlated with depression scores, but no other relationships were evident. The role of anti-phospholipid antibodies, anti- Ro antibodies, corticosteroid dose and confounds such as renal involvement in SLE, hypertension and motor speed differences were considered. None of these factors could explain cognitive dysfunction in the patient group. These findings are interpreted as indicating that cognitive performance in NPSLE is unlikely to be driven by emotional health. Instead performance related to white matter integrity and general illness, two factors which may be interlinked.

The first topic addressed in this thesis was the characterization of a new hybrid PET/CT scanner (Discovery-690); that was later used for all of the studies (experimental and clinical)performed in this work. Subsequently an antropomorphic static cardiac phantom is described. This was used to analyze the performances of different reconstruction algorithms, encompassing di fferent levels of information such as: i) the Time Of Flight (TOF) of the photons and ii) the Point-Spread-Function (PSF) of the PET tomograph. A problem, own of cardiac studies in PET, is the motion blur due to the cardiac beat and to the breath of the patient. To study the e ffects of this combined motion, both quantitatively and qualitatively, a moving mechanical phantom was built, that executed both movements in a separate and controlled way. After this investigation this phantom was exploited to evaluate the e cacy of gating techniques (cardiac and respiratory), by using single and double gating. These techniques were also applied to patient data. Double gating revealed to be able to provide better spatial resolution but with noise levels too high for diagnostic purposes. To overcome this problem while maintaining the full spatial resolution two registration techniques were proposed. The fi rst one consists in an affi ne registration that can be applied to correct only for respiratory motion. The second technique aims at registering all of the gates using an elastic morphing technique. This is achieved by using a map of the myocardial surface to build a Thin-Plate-Spline deformation field, using a segmentation algorithm. Both techniques allowed the reduction of the noise. In both phantom and patient studies promising quality improvements were obtained. The last chapter of the thesis involved the quanti cation of absolute cardiac perfusion analyzing 13NH3 PET studies with kinetic models. Initially the mathematical proprieties of the models proposed to analyze this tracer were assessed. Following the e ect of the image reconstruction algorithms on the parameters quanti ed with a speci c model were assessed. Two di erent software programs that allow perfusion quanti cation were also compared. The results of the studies described allowed the de nition of a clinical 13NH3 PET protocol, currently in use.

The production and distribution of counterfeit drugs is a critical health problem that plagues nations worldwide. The presence of counterfeit antimalarials has become especially worrying, as these drugs are most often needed by those living in nations whose resources to verify the medicine supply are lacking. Rapid analysis methods used for screening large quantities of poor quality antimalarials are critical in the battle to protect those in less developed regions of the world. Simple, cost effective analysis methods that can be used in the field must be developed so those whose governments cannot afford to maintain medicine regulatory agencies can still have faith in their medicinal supply. A very powerful screening method, Direct Analysis in Real Time Mass Spectrometry (DART-MS) has been used to investigate thousands of poor quality medicines. This method, however, is known to fragment molecules more readily than commonly used, 'softer' ionization methods, such as electrospray ionization. Excess fragmentation in 'harder' ionization sources is due to deposition of additional internal energy to the ionized molecules. This internal energy deposition can be measured, so the analyst can be knowledgeable as to what to expect when examining unknowns using this recently developed ionization source. Quantitation of the active pharmaceutical ingredient (API) in pharmaceuticals is crucial to the determination of what class a poor quality medicine fits into. Because poor quality drugs can be of different types, it is important to accurately classify them, in hopes of improving the supply of medicines available to those in less developed regions of the world. High performance liquid chromatography (HPLC) is most commonly used to quantify the active pharmaceutical ingredient in poor quality medicines, however, this method is time consuming, preventing its use in high throughput settings. During the course of my research, hundreds of poor quality pharmaceuticals were analyzed using DART-MS. The active pharmaceutical ingredient was detected during the rapid screening for many of these drugs, however, a more in depth analysis would often reveal less than the expected quantity of active ingredient. A rapid non-chromatographic quantitation method was developed using a mass spectrometer as the detector. This method allows for both quantitative and qualitative information regarding a specific sample to be obtained simultaneously, saving the analyst time and resources. Utilizing this non- chromatographic mass spectrometric method, degradation products have been identified, thus increasing our ability to classify drugs into their respective divisions.

A practical evaluation has been made of a methodology for quantitative evaluation of change in breast parenchymal density by computer analysis of digitised mammograms. It was hypothesised that interval changes in radiographic breast density could be quantified by a method of normalisation to a reference density on the mammograms, namely, the pectoralis major muscle. The bilateral lateral-oblique mammograms of ten patients at a two year interval were selected. These forty mammograms and calibrated test tools films were digitised using a charge-coupled device camera (CCD) and a drum-scanning microdensitometer (DSMD). The DSMD was found to be more suitable for this work due to the highly linear response characteristics, wide latitude of response, uniform and low noise levels, accurate film positioning and the possibility of more rapid image analysis. The CCD had a logarithmic linear response with less wide latitude, less uniform and higher noise levels, and variation introduced due inaccuracy in film positioning. For the DSMD, the difference between the breast region of interest (ROI) pixel value and pectoralis muscle ROI pixel value, was confirmed as the most appropriate for the method of normalisation; for the CCD, the ratio of logarithms was suitable. The importance of very meticulous mammographic technique was highlighted. Difficulties with normalisation were mostly due to non-uniform compression and inadequate inclusion of pectoralis muscle. For the DSMD images, a more rapid 'autotrace' method for outlining the pectoralis muscle ROI was comparable in accuracy to the slower method which took measurements from six small ROIs.

Magister Pharmaceuticae - MPharm
Diabetes mellitus is a complex chronic condition and has become a major public health concern worldwide. Many diabetic patients are accessing primary health care (PHC) clinics for diabetes care. Diabetic patients who are considered stable are referred to chronic diseases of lifestyle club at the PHC facility. Effective management of this chronic condition requires a multidisciplinary team approach to diabetes care. Pharmacists are not often included in a multidisciplinary team and would consist of doctors, nurses and dieticians. Teams may be expanded and require specialist healthcare members’ expertise who can assist in the management of this disease, for example, ophthalmologists and podiatrists. Adherence to standard treatment guidelines (STGs) for the management of diabetes by healthcare professionals at a primary care level can improve glycemic control, decrease health costs and reduce the development of long-term diabetic complications.

Drugs and other foreign compounds must often be metabolised before they can be excreted from the body. One enzyme system that is responsible for this is the cytochrome P450 gene family (CYP). In this thesis, new sensitive molecular techniques have been used to study the human gene expression of some CYP enzymes, as well as the P-glycoprotein transporter (P-gp). The aim was to evaluate whether tissues other than the liver, e.g. the blood, could be used to assess an individual's drug metabolic capacity. Another aim was to investigate the gene expression in relation to the liver transplant process and a third aim was to evaluate the expression in gastrointestinal mucosa in both normal and inflamed mucosa.

We evaluated the CYP gene expression in paired specimens of liver and blood but found no correlation in the expression patterns of these two tissues. Instead, we found the opposite pattern, where, for example, CYP1B1 had the highest expression in the blood but the lowest in the liver and CYP2E1 was the enzyme with the highest expression in the liver. In an investigation of the expression of four different CYP enzymes and P-gp in liver transplants before and during the first year after transplantation, we found that the levels of all the CYP enzymes but not P-gp increased with time. We also found that the expression of CYP3A4 was inversely related to the normalised plasma levels of the immunosuppressive drugs cyclosporine and tacrolimus.

In the gastrointestinal tract, CYP2E1 was the enzyme with the highest mRNA expression compared with CYP3A4, CYP3A5 and the transporter P-gp. CYP3A4 has its highest expression in the duodenum compared with the expression in the stomach and the colon. CYP3A5 is expressed at a higher level than CYP3A4 in the colon. P-gp expression levels increase through the gastrointestinal tract to the left colon. Gene expression levels of CYP2E1 and CYP3A4 decrease in severely inflamed rectal mucosa.

In conclusion, this is a sensitive method for studying gene activity in a clinical situation, even though at this point we are not able to use blood or gastrointestinal mucosa as “surrogate” tissue to estimate an individual’s drug metabolic capacity. The studies in liver transplants and gastrointestinal mucosa are unique in that the gene expression is investigated during a clinical course of events.