Genetic Screening of LCA in Belgium: Predominance of CEP290 and Identification of Potential Modifier Alleles in AHI1 of CEP290-Related Phenotypes

Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.

Identification of mechanisms controlling the transcriptional activity of nuclear factor kappa B (NF-��B) p65/RelA

Disserta����o para a obten����o do grau de doutor em Biologia pelo Instituto de Tecnologia Qu��mica e Biol��gica. Universidade Nova de Lisboa.

Immunocytochemical identification of leishmania and Trypanosoma cruzi amastigotes in situ with homologous and heterologous polyclonal antibodies

The unlabelled antibody peroxidase-antiperoxidase method was used to study the immunocytochemical properties of Leishmania and Trypanosoma cruzi amastigotes in situ after tissues had been submitted to different fixation procedures. Antisera were obtained from rabbits chronically infected with different strains of T. cruzi or immunized with L. mexicana amazonensis and L. braziliensis guyanensis, and were applied on 5 ��m thick sections. T. cruzi antigens were well stained by the three anti-T. cruzi sera and the two anti-heis.hmama.sera at optimum dilution between 1:1,000 and 1:2,000, regardless the parasite strain. Differently, the leishmanial antigens were revealed by Leishmania sera only at low dilutions (between 1:60 -1:160), whereas the anti-T. cruzi sera, at these low dilutions, gave rather weak stainings. Although there is no clear explanation for this immunocytochemical "reverse-monodirectional" cross-reactivity between Leishmania and T. cruzi, the present results show that polyclonal antibodies agains Leishmania species, when used for immunocytochemical detection of these parasites in situ, react more strongly with T. cruzi amastigotes than with the homologous amastigotes.

Regulation of the rice gene OsRMC under salt stress: identification and functional characterization of novel transcription factors

Dissertation presented to obtain the Ph.D degree in Biology

Recursive neuro fuzzy techniques for online identification and control

Disserta����o para obten����o do Grau de Mestre em Engenharia Electrot��cnica e de Computadores

Osmo- and thermo-adaptation in hyperthermophilic Archaea: identification of compatible solutes accumulation profiles, and biosynthetic routes in Archaeoglobus spp.

Dissertation presented to obtain the Ph.D degree in Biochemistry

Quantification and characterization of the phenolic compounds of kenaf leaves

Dissertation for the Master Degree in Technology and Food Security

Compact ion-source based on superionic rubidium silver iodide (RbAg4I5) solid electrolyte

Disserta����o para obten����o do Grau de Mestre em Engenharia F��sica

Identification of atmospheric pollutants control mechanisms during co-combustion of coal and non-toxic wastes

Doctoral dissertation for Ph.D. degree in Sustainable Chemistry

O erro na fase pr��-anal��tica : amostras n��o conformes versus procedimentos

RESUMO: As An��lises Cl��nicas s��o um precioso elemento entre os meios complementares de diagn��stico e terap��utica permitindo uma enorme pan��plia de informa����es sobre o estado de sa��de de determinado utente. O objetivo do laborat��rio �� fornecer informa����o anal��tica sobre as amostras biol��gicas, sendo esta caracterizada pela sua fiabilidade, relev��ncia e facultada em tempo ��til. Assim, tratando-se de sa��de, e mediante o prop��sito do laborat��rio, �� not��ria a sua import��ncia, bem como, a dos fatores associados para o cumprimento do mesmo. O bom desenrolar do ciclo laboratorial, compreendido pelas fases pr��-anal��tica, anal��tica e p��s-anal��tica �� crucial para que o objetivo do laborat��rio seja cumprido com rigor e rapidez. O presente trabalho ���O Erro na Fase Pr��-Anal��tica: Amostras N��o Conformes versus Procedimentos���, enquadrado no mestrado de Qualidade e Organiza����o no Laborat��rio de An��lises Cl��nicas, pretendeu enfatizar a import��ncia da fase pr��- anal��tica, sendo ela apontada como a primordial em erros que acabam por atrasar a sa��da de resultados ou por permitir que os mesmos n��o sejam fidedignos como se deseja, podendo acarretar falsos diagn��sticos e decis��es cl��nicas erradas. Esta fase, iniciada no pedido m��dico e finalizada com a chegada das amostras biol��gicas ao laborat��rio est�� entregue a uma diversidade de procedimentos que acarretam, por si s��, uma grande diversidade de intervenientes, para al��m de uma variabilidade de factores que influenciam a amostra e seus resultados. Estes fatores, que podem alterar de algum modo a ���veracidade��� dos resultados anal��ticos, devem ser identificados e tidos em considera����o para que estejamos convitos que os resultados auxiliam diagn��sticos precisos e uma avalia����o correta do estado do utente. As colheitas que por quaisquer diverg��ncias n��o originam amostras que cumpram o objectivo da sua recolha, n��o estando por isso em conformidade com o pretendido, constituem uma importante fonte de erro para esta fase pr��-anal��tica. Neste estudo foram consultados os dados relativos a amostras de sangue e urina n��o conformes detetadas no laborat��rio, em estudo, durante o 1�� trimestre de 2012, para permitir conhecer o tipo de falhas que acontecem e a sua frequ��ncia. Aos T��cnicos de An��lises Cl��nicas, colaboradores do laborat��rio, foi-lhes pedido que respondessem a um question��rio sobre os seus procedimentos quotidianos e constitu��ssem, assim, a popula����o desta 2�� parte do projeto. Preenchido e devolvido de forma an��nima, este question��rio pretendeu conhecer os procedimentos na tarefa de executar colheitas e, hipoteticamente, confront��-los com as amostras n��o conformes verificadas. No 1��semestre de 2012 e num total de 25319 utentes registaram-se 146 colheitas que necessitaram de repeti����o por se verificarem n��o conformes. A ���amostra n��o colhida��� foi a n��o conformidade mais frequente (���50%) versus a ���m�� identifica����o��� que registou somente 1 acontecimento. Houve ainda n��o conformidades que n��o se registaram como ���prepara����o inadequada��� e ���amostra mal acondicionada���. Os t��cnicos revelaram-se profissionais competentes, conhecedores das tarefas a desempenhar e preocupados em execut��-las com qualidade. Eliminar o erro n��o estar��, seguramente, ao nosso alcance por��m admitir a sua presen��a, detet��-lo e avaliar a sua frequ��ncia far�� com que possamos diminuir a sua exist��ncia e melhorar a qualidade na fase pr��-anal��tica, atribuindo-lhe a relev��ncia que desempenha no processo laboratorial.-----------ABSTRACT:Clinical analyses are a precious element among diagnostic and therapeutic tests as they allow an enormous variety of information on the state of health of a user. The aim of the laboratory is to supply reliable, relevant and timely analytical information on biological samples. In health-related matters, in accordance with the objective of the laboratory, their importance is vital, as is the assurance that all the tools are in place for the fulfillment of its purpose. A good laboratory cycle, which includes the pre-analytical, analytical and post-analytical phases, is crucial in fulfilling the laboratory���s mission rapidly and efficiently. The present work - "Error in the pre-analytical phase: non-compliant samples versus procedures���, as part of the Master���s in Quality and Organization in the Clinical Analyses Laboratory, wishes to emphasize the importance of the pre-analytical phase, as the phase containing most errors which eventually lead to delays in the issue of results, or the one which enables those results not to be as reliable as desired, which can lead to false diagnosis and wrong clinical decisions. This phase, which starts with the medical request and ends with the arrival of the biological samples to the laboratory, entails a variety of procedures, which require the intervention of different players, not to mention a great number of factors, which influence the sample and the results. These factors, capable of somehow altering the ���truth��� of the analytical results, must be identified and taken into consideration so that we may ensure that the results help to make precise diagnoses and a correct evaluation of the user���s condition. Those collections which, due to any type of differences, do not originate samples capable of fulfilling their purpose, and are therefore not compliant with the objective, constitute an important source of error in this pre-analytical phase. In the present study, we consulted data from non-compliant blood and urine samples, detected at the laboratory during the 1st quarter of 2012, to find out the type of faults that happen and their frequency. The clinical analysis technicians working at the laboratory were asked to fill out a questionnaire regarding their daily procedures, forming in this way the population for this second part of the project. Completed and returned anonymously, this questionnaire intended to investigate the procedures for collections and, hypothetically, confront them with the verified non-compliant samples. In the first semester of 2012, and out of a total of 25319 users, 146 collections had to be repeated due to non-compliance. The ���uncollected sample��� was the most frequent non-compliance (>50%) versus ���incorrect identification��� which had only one occurrence. There were also unregistered non-compliance issues such as ���inadequate preparation��� and ���inappropriately packaged sample���. The technicians proved to be competent professionals, with knowledge of the tasks they have to perform and eager to carry them out efficiently. We will certainly not be able to eliminate error, but recognizing its presence, detecting it and evaluating its frequency will help to decrease its occurrence and improve quality in the pre-analytical phase, giving it the relevance it has within the laboratory process.

Credit cycle identification: A Markov-switching application

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA ��� School of Business and Economics

In-School CSR and its impact on brand image, brand identification and brand reputation: The moderator effect of brand familiarity, product involvement and cause-brand fit

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA ��� School of Business and Economics

Identification of Leishmania chagasi from skin in Leishmania/HIV co-infection: a case report

A case of HIV/Leishmania co-infection presenting both visceral and cutaneous manifestations is reported. Leishmania infection was confirmed by conventional methods (parasitological approach and serology) and by PCR. Leishmania chagasi isolated from the skin lesion was characterized by enzyme electrophoresis and by restriction fragment length polymorphism of the internal transcribed spacer of the ribosomal gene.