Tesis sobre el tema "Test olfactif"

Dans cette thèse nous avons créé un test olfactif et vérifié son utilité pour dépister des troubles en lien avec la pathologie d'Alzheimer ou celle de l'apathie, ou encore dans la COVID-19.Après avoir recueilli l'avis des cliniciens et les recommandations des experts chimistes, nous avons ensuite sélectionné quatorze odeurs, mis au point un test olfactif informatisé qui permet d'obtenir automatiquement le score de seuil de perception et d'identification. Ce travail a permis le dépôt d'un Brevet d'invention pour le "Test Olfactif de Dépistage de la maladie d'Alzheimer et de l'apathie", ou TODA.Nous avons vérifié l'intérêt du TODA en pratique de soins courants dans l'aide au diagnostic de la maladie d'Alzheimer auprès de malades d'Alzheimer en contrôles sains, en France et au Québec. Les scores olfactifs différenciaient très significativement les sujets et étaient corrélés à la mesure cognitive globale. Le TODA permettait aussi de repérer une identification des odeurs différente en fonction de la culture et de la pathologie.Dans une population de sujets présentant un Trouble Cognitif Mineur avec ou sans apathie, les résultats au TODA permettaient de différencier les sujets très significativement, notamment dans la sous-dimension sociale des critères de l'Apathie.Auprès de sujets présentant une post-infection à la COVID-19, le TODA a été utilisé en parallèle du Sniffin'Sticks Test, gold-standard actuel, pour vérifier la validité des résultats du TODA. Le TODA a aussi permis de mettre en évidence des confusions d'odeurs proches, révélant une atteinte de leurs propriétés olfactives. Son utilisation en cas de suspicion d'atteinte sémantique associée a elle aussi été concluante.La comparaison des scores obtenus au TODA par les sujets MA et par les sujets post-COVID-19 a révélé que les résultats étaient similaires. Seule l'étude des odeurs les plus significatives a permis de faire la différence entre les deux pathologies
In this thesis we created an olfactory test to measure its usefullness to detect disorders such as Alzheimer's disease or apathy syndrome or COVID-19.First, we collected the opinions of clinicians and the recommendations of experts chemists. We then selected fourteen odors, and we developed a computerized olfactory test that was able to calculate threshold and identification automatically using theses odors. We submitted a Patent for this test named "Olfactory Test for screening Alzheimer's disease ans apathy" (TODA).We cerified the interest ol TODA in everyday care practice in the diagnosis of Alzheimer's disease. Using subjects with Alzheimer's disease and healthy control subjects, both in France and Quebec, the test scores significantly differenciate AD subjects from control subjects. This test allowed cognitive monitoring of patients and highlighted odor identification regardless of culture and pathology.With a population of subjects with Minor Cognitive Disorder, with and without apathy, the results were able to significantly differenciate subjects, in particular, with a social sub-dimension of Critéria of Apathy.With subjects suffering from post-COVID-19 infection we tested with the TODA and in parallel we used the Sniffin' Stick Test, a gold standard, to verify the validity of the TODA results. The TODA also allowed us to highlight the problems identify similar odors. Finally, we also highlighted the interest of using the TODA in the case of suspected associated semantics impairment.The comparison of the TODA scores obtained by AD subjects and COVID-19 subjects showed that there was no difference between the two groups. Only the study of the most significant odors made it possible to differenciate between the two patologies

Dans la schizophrénie, de nombreux patients présentent un manque de soins d’hygiène personnelle, caractéristique du versant négatif de la symptomatologie. Cette négligence donne naissance à une odeur corporelle nauséabonde, qui d’antan fut un élément déterminant du diagnostic. Les prises en charge de ce symptôme, focalisées sur les soins fondamentaux de la toilette, sont souvent une gageure et échouent. En nous inscrivant dans une démarche pluridisciplinaire, nous tentons de donner du sens aux odeurs corporelles dans la schizophrénie. Notre hypothèse est que les comportements d’hygiène personnelle pourraient être conditionnés par les capacités du système olfactif des patients, sujet tout juste effleuré jusqu’ici. Une épreuve d’identification d’échantillons odorants au moyen d’images photographiques des sources d’odeurs potentielles a été normalisée : le test olfacto-visuel (TOV). L’application du TOV a permis de montrer un défaut des capacités d’identification olfactive chez les patients, sa relation avec la symptomatologie et les compétences sociales des patients. La mise en place d’un atelier thérapeutique à médiation olfactive a conduit à montrer les conséquences bénéfiques de la prise en charge de la sensorialité olfactive sur l’évolution des capacités olfactives, la symptomatologie, les comportements hygiéniques et alimentaires ainsi que sur le vécu affectif des patients atteints de schizophrénie. Ces derniers montrent aussi des dysfonctionnements de la sphère émotionnelle. Nous avons d’abord réanalysé les liens existants entre la caractéristique hédonique des odorants et les émotions dans la population générale, puis repoussé leurs simplifications habituelles. Les liens entre odeurs perçues et émotions évoquées par les échantillons odorants apparaissent perturbés chez les patients. Ce travail de recherche propose une relecture de la perception olfactive dans la schizophrénie et montre l’intérêt thérapeutique de son exploitation. L’évolution clinique positive des comportements d’hygiène personnelle, après la prise en charge olfactive, valide l’hypothèse du rôle de l’odeur corporelle en tant que gardien de l’existence. L’ « être-au-monde odorant » des patients possède une fonction identitaire dans la schizophrénie
In the case of schizophrenia, numerous patients have poor personal hygiene, which is typical of negative symptomatology. This self-neglect engenders offensive body odor which also was in the past a crucial element for the diagnosis. Attempts to address the manifestations of that symptom by focusing on the principles of basic grooming often prove a losing battle and fail. Thanks to an interdisciplinary approach, our endeavor is to try and give meaning to body odor for schizophrenics. Our hypothesis is that personal hygiene behavior could be conditioned by the patients’ olfactory system capacities – a domain which has barely been studied to this day. An olfactory stimuli identification test of potential odor sources via photographic images has been standardized: the olfacto-visual test (OVT). The OVT’s application has permitted to reveal an olfactory identification deficit in the patients, its relation to symptomatology and the patients’ social skills. The setting up of a therapeutic workshop through olfactory mediation has led to show the beneficial consequences of the caring for the sense of smell on the evolution of olfactory skills, symptomatology, hygiene and dietary patterns, as well as on the patients’ emotional life. Patients suffering from schizophrenia also present emotion-management troubles. We have first analyzed the existing links between the hedonic characteristics of odorants and the emotions among the general population anew, and then questioned the usual simplifications about them. The links between perceived odors and emotions produced by the odor samples appeared as blurred for the patients. This research offers a new approach of the olfactory perception in schizophrenia and shows the therapeutic interest of its exploitation. The positive clinical evolution of personal hygiene behavior after the olfactory caring confirms the hypothesis of the role of body odor as a token of existence. The patients’ bad body odor reveals an identity function in schizophrenia

Orientador: Maria Aparecida Azevedo Pereira da Silva
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: Testes sensoriais para a avaliação da função olfatória de indivíduos têm sido validados e utilizados em diagnósticos da população em geral, e em portadores de desordens cerebrais e pesquisas em neurociência em particular. No Brasil, testes para serem utilizados com segurança e eficiência para a avaliação da capacidade de identificação e discriminação de odores de indivíduos ainda não foram adequadamente desenvolvidos e validados. Assim, os objetivos da presente pesquisa foram: i) desenvolver, testar e validar testes de identificação e discriminação de odores para avaliar a função olfatória de indivíduos brasileiros, ii) avaliar a potencialidade das metodologias desenvolvidas para uso em pré-diagnóstico clínico de indivíduos da terceira idade e pacientes portadores de epilepsia, iii) verificar o desempenho, em portadores de epilepsia, de uma metodologia já validada e utilizada mundialmente para avaliar a capacidade de identificação de odores de indivíduos e, iv) avaliar em portadores de epilepsia, funções que são processadas por substratos neurais comuns à função olfatória, neste caso, a capacidade de reconhecimento de emoção facial e vocal. Para o teste de identificação de odores, foi desenvolvido um instrumento intitulado "Pastilhas de Odor¿ contendo em pastilhas individuais, 36 odores familiares aos brasileiros. Os odores foram caracterizados quanto à intensidade, aceitação, pungência, refrescância e familiaridade, sendo considerados adequados para comporem um teste de avaliação da função olfatória. A identificação dos odores de "Pastilhas de Odor¿ foi realizada através de um teste de múltipla escolha contendo quatro alternativas, das quais apenas uma é a correta. Para o desenvolvimento do teste de discriminação de odores, 24 voláteis odoríferos puros (P.A.), associados a 6 diferentes categorias de odor - doce, verde, frutal, cítrico, floral e desagradável - foram selecionados e diluídos em propilenoglicol. Com essas amostras, 36 testes de comparação pareada foram construídos, onde em cada categoria de odor, uma amostra alvo foi selecionada para ser comparada com as demais da mesma categoria. O desempenho de cada indivíduo neste teste é analisado utilizando-se a teoria "signaldetection¿, através dos seguintes parâmetros: taxa de acertos (HR), taxa de falsos alarmes (FR), poder discriminativo (d¿L) e vício de resposta (CL). Os dois testes desenvolvidos - "Pastilhas de Odor¿ e teste de discriminação - foram validados com a participação de três grupos de indivíduos: grupo controle, grupo da terceira idade e grupo de indivíduos portadores de epilepsia do lobo temporal (ELT). A capacidade de identificação de odores, de pacientes norte-americanos portadores de ELT foi também avaliada, utilizando-se com esse fim, o teste já validado, denominado "University of Pennsylvania Smell Identification Test¿ (UPSIT), o qual consiste em um teste de múltipla escolha, composto por 40 estímulos odoríferos microencapsulados. Adicionalmente, avaliou-se nesses pacientes, a capacidade de reconhecimento de emoção facial e vocal, utilizando-se uma nova ferramenta intitulada "Comprehensive Affect Testing System¿ (CATS). Com relação à capacidade de identificação de odores dos indivíduos brasileiros, os resultados obtidos através do teste "Pastilhas de Odor¿ revelaram significância estatística tanto para o efeito "sexo¿ (p=0,0003), como para o efeito "idade¿ (p<0,001). O teste também permitiu identificar que os portadores de ELT, sem cirurgia e após ressecção do lobo temporal, apresentavam menor capacidade de identificação de odores comparativamente ao grupo controle (p= 0,05); este mesmo resultado foi observado ao aplicar o UPSIT em portadores de ELT norte-americanos, antes e após os mesmos terem sido submetidos à mencionada cirurgia. O teste "Pastilhas de Odor¿ mostrou ser de fácil manuseio e aplicação em indivíduos adultos, apresentou alto coeficiente de confiabilidade no teste-reteste (r=0,87, p<0,001) e suas pastilhas apresentaram boa estabilidade ao armazenamento durante 3 meses. Por sua vez, os dados obtidos através do teste de discriminação de odores identificaram que tanto o grupo da terceira idade como o dos portadores de ELT apresentaram poder discriminativo e taxa de acertos inferiores (p=0.05) aos indivíduos do grupo controle. Os resultados obtidos pela aplicação do teste CATS em indivíduos norte-americanos, revelaram que pacientes ELT tanto pré- como póscirúrgicos apresentaram menor reconhecimento de emoção facial e vocal quando comparados com o grupo controle, principalmente para as emoções negativas. O fato dos testes "Pastilhas de Odor¿ e de discriminação de odores desenvolvidos na presente pesquisa terem detectado deficiência olfatória nos indivíduos brasileiros da terceira idade e portadores de epilepsia, constrói validade para a utilização dos mesmos em diagnósticos clínicos associados a essas populações
Abstract: Sensory tests to evaluate olfactory function have been validated and used in the diagnosis of subjects, mainly in brain disorders patients, and in the neuroscience research. In Brazil, reliable tests of odor discrimination and identification have not been appropriately developed and validated. The aims of the present study were: i) to develop, test and validate odor discrimination and identification tests to assess olfactory function of Brazilian population; ii) to evaluate the methodologies performance in the diagnosis of elderly subjects and epilepsy patients. For odor identification test, the developed instrument was entitled "Odor Tablets¿, with 36 different odors familiar to Brazilians; to verify the performance in patients with epilepsy, a methodology previously validated and used worldwide to evaluate the ability to identify odors of individuals, and iv) to evaluate in patients with epilepsy, functions that are processed by common neural substrates for olfactory function, in this case, the ability of recognition of voice and facial emotion. Odors were rated as to their intensity, pleasantness, pungency, coolness and familiarity and they were considered suitable for composing a test to assess olfactory function. "Odor Tablets¿ proceeded through multiple-choice test with four alternatives which only one was correct. For the development of odor discrimination test, 24 pure odorants, associated with six different odor categories ¿ sweet, green, fruity, citric, floral and unpleasant - were selected and diluted in propylene glycol. With these samples, 36 paired comparison tests were constructed, where in each odor category, a target sample was selected to be compared with the others in the same category. The participant¿s performance in the odor discrimination test was analyzed using the "signal-detection" theory through the following parameters: hit rate (HR), false-alarm rate (FR), discrimination measurement (d 'L) and bias response (CL). Both tests, "Odor Tablets¿ and odor discrimination test, were validated with three groups of subjects: control group, elderly group and temporal lobe epilepsy patients group (TLE). The ability to identify odors from North American TLE patients was also measured, using for this purpose, the validated test "University of Pennsylvania Smell Identification Test" (UPSIT), a multiple choice test consisting of 40 microencapsulated odor stimuli. In addition, the ability of recognition of voice and facial emotion of TLE patients were evaluated using a new tool entitled "Comprehensive Affect Testing System" (CATS). For the subject¿s ability to identify odors, there were significant differences for gender (p=0.0003) and age (p<0.001). Also, for this test, the results showed that pre- and postsurgery epilepsy patients presented lower performance than the control group (p= 0.05); This same result was observed when applying the UPSIT in American TLE patients before and after surgery. "Odor Tablets¿ proved to be easy to administer in adult subjects, showed a high coefficient of the test-retest reliability (r = 0.87, p<0.001), and the tablets presented a storage stability for 3 months. The discrimination test results showed that elderly and epilepsy patient groups presented lower performance in the discrimination measurement and hit rate parameters than the control group. The results obtained using the CATS test in American TLE patients revealed that both pre-and post-surgery showed deficits in the facial and vocal emotions when compared with the control group, especially for negative emotions. The fact that the "Odor Tablets¿ and the discrimination odor test developed in the present study had detected olfactory dysfunction in elderly subjects and epilepsy patients, provides their validity for use in the diagnoses of these population
Doutorado
Consumo e Qualidade de Alimentos
Doutor em Alimentos e Nutrição

This research involves an examination of the olfactory ability of individuals with Frontotemporal Dementia, Alzheimer's disease, and geriatric individuals with cognitive complaints owing to Major Depressive Disorder or Generalized Anxiety Disorder. The purpose of this study was to determine if olfactory differences were useful in differentiating between demented and non-demented individuals. Due to the pathway of the olfactory tract, it can be expected that there would be equal olfactory deficits in those diagnosed with Frontotemporal Dementia and Alzheimer's disease, and that these deficits would be worse than those found in geriatric individuals with Major Depressive Disorder or Generalized Anxiety Disorder. Five hypotheses were investigated. The first utilized an ANCOVA and found that the olfaction of the demented group was worse than that of the non-demented, psychiatric group. The second utilized a series of Discriminant Function Analyses and F-tests and determined that olfaction best classified demented and non-demented individuals. The third implemented a Mixed Model ANOVA to assess for lateralized smell deficits within the demented group and between the demented and non-demented groups and found no main effects of lateralization or interaction effects. The fourth hypothesis investigated the relationship between smell and commonly used neuropsychological tests in a Frontotemporal Dementia sample, and found that there was no difference between the relationship of tests measuring the frontal and temporal lobes to those measuring other cerebral areas. The fifth hypothesis replicated Hypothesis 4 in an Alzheimer's disease sample and found that there was a significant difference between the relationship of tests measuring the frontal and temporal lobes to those measuring other cerebral areas. Primarily, this study demonstrated that dementia patients present with significantly more olfactory deficits than a psychiatric sample with subjective cognitive complaints. Additionally, olfaction correctly distinguished the Dementia Group from the Psychiatric Group with 81.6% accuracy, 90.2% sensitivity and 67.6% specificity. Alone, these classification statistics are quite impressive, appearing equivalent, or possibly superior to the classification statistics of commonly used neuropsychological tests of memory, executive functioning, and visuospatial ability. This study concluded that adding an olfactory measure to an assessment battery provides clinically relevant data, and enhances the diagnostic accuracy of the battery. However, though this study found the Alberta Smell Test was a valuable addition to a test battery, the absence of lateralized findings demonstrated the unirhinal format, by which the Alberta Smell Test is administered, does not provide diagnostically relevant information above and beyond the information a clinician will gain from birhinal assessment.

Orientador: Laura Silveira Moriyama
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A olfação encontra-se comprometida em várias doenças neurodegenerativas no adulto, mas os conhecimentos sobre perda olfativa em crianças são escassos. O teste de 16 odores do Sniffin' Sticks (SS16) é um dos mais utilizados mundialmente para testagem de identificação de cheiros, e já foi validado para adultos no Brasil. O objetivo deste estudo foi realizar uma adaptação do SS16 para a população infantil do Brasil e observar a influência de idade, sexo, rinite, nível socioeconômico e aspectos cognitivos sobre a performance no teste. Adaptações foram realizadas no teste para torná-lo mais familiar ao universo infantil, criando uma versão chamada SS16-Child. Além disso, um teste de identificação de figuras (PIT-SS16-Child) foi utilizado para avaliar aspectos cognitivos relacionados ao SS16-Child, como reconhecimento de figuras, nomeação e familiaridade com os 16 itens do teste. A versão final do teste foi então aplicada em 51 crianças, com idade média de 9.9 anos (variação 3-18 anos, desvio padrão= 4.25). Os dados demonstraram que os 16 odores foram facilmente identificados por crianças acima de 10 anos, e que mesmo para crianças pré-escolares (abaixo de 6 anos), pelo menos 5 itens foram altamente reconhecíveis (acima de 75% de reconhecimento). Não foi demonstrado efeito de sexo, rinite e nível socioeconômico sobre o teste de olfato. Os dados mostraram uma forte associação entre idade e performance no SS16-Child (r²=0.426, p<0.001), além de uma forte associação entre o idade e o resultado do PIT-SS16-Child (r2=0.436, p<0.001), que por sua vez também está associado com o desempenho no SS16-Child (p<0.001, r²=0.741). Análises multivariadas mostraram que o efeito da idade (p<0.05; B=0.171) e desempenho no PIT-SS16-Child (p<0.001; B=1.57) foram independentes quando ajustados estatisticamente um para o outro. Concluímos que o SS16-Child pode ser utilizado com adaptações para a população pediátrica brasileira, e que a interpretação dos resultados deve levar em consideração a idade do sujeito, e também seu desempenho no PIT-SS16-Child
Abstract: Olfaction is impaired in several neurodegenerative diseases in adults, but knowledge about olfactory loss in children is scarce. The 16 odors Sniffin' Sticks test (SS16) is the most widely used test of smell identification worldwide, and has been validated for adults in Brazil. The objective of this study was to adapt the SS16 to the pediatric population in Brazil and to study the influence of age, sex, rhinitis, socioeconomic status and cognitive performance on the test. Adjustments were made in the test to make it more familiar to the child's universe, creating a version called SS16-Child. In addition, a picture identification test (PIT-Child-SS16) was used to evaluate the cognitive aspects involved, including recognition of figures, naming and familiarity with 16 test items. The final version of the test was then applied in 51 children with a mean age of 9.9 years (range 3-18 years, standard deviation= 4.25). The data showed that the 16 odors were easily identified by children over 10 years, and even for preschool children (under 6 years) at least 5 items were highly recognizable (over 75% recognition). No effects of sex, rhinitis and socioeconomic status on the smell test were observed. The data showed a strong association between age and performance in SS16-Child (r²=0.426, p<0.001), and a strong association between age and the result of the PIT-SS16-Child (r2=0.436, p<0.001), which in turn was also associated with performance on the SS16-Child (p<0.001, r²=0.741). Multivariate analysis showed that the effect of age (p<0.05; B=0.171) and performance in the PIT-SS16-Child (p<0.001; B=1.57) were statistically independent when adjusted to one another. We conclude that the SS16-Child can be used with adaptations for the Brazilian pediatric population, and the interpretation of results must take into account the age of the subject, and also their performance in the PIT-SS16-Child
Mestrado
Ciencias Biomedicas
Mestra em Ciências Médicas

Meerkats are known to strongly rely on chemical communication in social contexts. However, little is known about their use of the sense of smell in food detection and selection. The aim of the present study was therefore to assess whether meerkats are able to (1) detect hidden food using olfactory cues, (2) distinguish the odour of real food from a single food odour component, and (3) build an association between the odour of real food and a novel odour. I employed the buried food test, widely used with rodents to assess basic olfactory abilities, designed to take advantage of the propensity of meerkats to dig. I found that the meerkats were clearly able to find all four food types tested (mouse, chicken, mealworm, banana) using olfactory cues alone and that they successfully discriminated between the odour of real food and a food odour component. In both tasks, the animals dug in the food-bearing corner of the test arena as the first one significantly more often than in the other three corners, suggesting development of an efficient foraging strategy. No significant association-building between a food odour and a novel odour was found within the 60 trials performed per animal. I conclude that meerkats are able to use olfactory cues when foraging and that their sense of smell is well-adapted for recognizing specific odours of behavioural relevance. To the best of my knowledge, this is the first study to successfully employ the buried food test with a carnivore species.

INTRODUÇÃO: Apesar da fundamental importância da olfação para avaliação dos sabores dos alimentos ingeridos, percepção de vazamento de gases e de incêndios, sua avaliação clínica ainda não se encontra padronizada no Brasil. O Teste de Identificação do Olfato da Universidade da Pensilvânia (UPSIT) é um teste mundialmente utilizado e considerado por muitos como o padrão-ouro da avaliação olfatória. Originalmente em inglês, já foi traduzido para mais de 12 línguas. Esse trabalho se propôs a validar de forma inédita o UPSIT para outra cultura. O UPSIT versão em português foi validado para a população brasileira e tabelas normativas foram elaboradas para comparação do escore obtido segundo o sexo e idade do indivíduo. Secundariamente, procurou-se os fatores preditores de um melhor escore no teste. CASUÍSTICA E MÉTODOS: Estudo transversal realizado de dezembro de 2011 a agosto de 2012. A amostra utilizada foi não-probabilística por quotas e constituída por indivíduos presentes em uma instituição de atendimento público (Poupatempo São Paulo), de forma consecutiva, sem queixas olfatórias no dia do exame. Foi determinada a quota de 60 brasileiros(as) em cada faixa etária de cada sexo, a saber: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55-59, 60-64, 65-69, 70-74, 75-79 e >= 80 anos. Após responderem questionário referente a dados demográficos e critérios de inclusão e exclusão do estudo, fizeram o UPSIT 782 indivíduos do sexo masculino e 796 do sexo feminino. Nos pacientes com idade igual ou superior a 65 anos foi realizado o Mini Exame do Estado Mental e se excluíram aqueles pacientes com escore inferior a 24 pontos pela possibilidade de quadro demencial. A versão do UPSIT aplicada nesse estudo foi resultado de dois estudos prévios para melhorar a aplicabilidade desse teste para a população brasileira. RESULTADOS: 1820 voluntários participaram do estudo, 1578 foram incluídos nas tabelas normativas. 242 foram excluídos no dia da entrevista por estarem com infecção das vias aéreas superiores, terem história de trauma crânio-encefálico, queixa de perda de olfato ou paladar e um escore menor de 24 no Mini Exame do Estado Mental. Verificou-se que entre os 1578 indivíduos analisados, o escore de UPSIT variou de 9 a 40, obtendo-se escore médio de 32,1 (desvio padrão: 5,3) e escore mediano igual a 33. Pela análise univariada (p < 0,01) e multivariada - regressão linear múltipla- (p < 0,05), observou-se que a idade, sexo, número de anos de estudo e renda mensal da família influíram no escore do teste. CONCLUSÕES: O UPSIT está agora validado para utilização na população brasileira. Disponibilizou-se tabelas normativas para avaliação olfatória e um modo rápido de obtê-las. Fatores de correção são necessários para uma perfeita equivalência entre as normas de todos os continentes, utilizando como padrão-ouro as normas do país onde a versão original do teste foi desenvolvida. Pior status econômico e educacional interferem negativamente na performance olfatória
INTRODUCTION: Despite the fundamental importance of olfaction to assess the flavors of food, perception of gas leakage and fire, its clinical evaluation is not yet standardized in Brazil. The University of Pennsylvania Smell Identification Test of the (UPSIT) is a test used worldwide and considered by many as the gold standard of olfactory assessment. Originally in English, it has been translated into more than 12 languages. This study aimed to validate the UPSIT for another culture in a novel form. The portuguese version of UPSIT Portuguese version was validated for the Brazilian population and normative tables were prepared to compare the score obtained by sex and age of the individual. Secondarily, we sought the predictors of a better score on the test. PATIENTS AND METHODS: Cross-sectional study conducted from December 2011 to August 2012. The sample used was a non-probabilistic by quotas and consisted of individuals present in a public service institution (Poupatempo São Paulo), consecutively, without olfactory complaints on exam day. We determined the quota of 60 Brazilians in each age group for each sex, as follows: 20-24, 25-30, 31-34, 35-40, 41-44, 45-50, 50-54, 55 -59, 60-64, 65-69, 70-74, 75-79 and >= 80 years. After answering a questionnaire about demographics and inclusion and exclusion criteria of the study, 782 males and 796 females did the UPSIT. In patients aged over 65 years was held the Mini Mental State Examination and excluded those patients with a score less than 24 points for the possibility of dementia. The version of the UPSIT applied in this study was the result of two previous studies to enhance the applicability of this test for the Brazilian population. RESULTS: 1820 volunteers participated in the study, 1578 were included in the normative tables. 242 were excluded on the day of the interview for being with upper airway infection, having an history of head trauma, complaining of smell or taste losses and a score below 24 on the Mini Mental State Examination. It was found that among the 1578 subjects analyzed, the UPSIT scores ranged from 9 to 40, yielding a mean score of 32.1 (SD: 5.3) and a median 33. By univariate analysis (p < 0.01) and multivariate analysis - multiple linear regression-(p < 0.05), it was observed that the age, sex, years of schooling and family monthly income influenced the test scores. CONCLUSIONS: UPSIT is now validated for use in the Brazilian population. Normative tables for olfactory assessment and a fast way to obtain them were demonstrated. Correction factors are needed for a perfect equivalence between norms of all continents, using as gold standard norms of the country where the original version of the test was developed. Worse economic and educational status interfered negatively in olfactory performance

Le système nerveux central est isolé de l’environnement grâce à un ensemble de barrières, incluant la barrière osseuse et la barrière hémato-encéphalique. Il existe cependant des zones où ces barrières sont absentes ou affaiblies, et c’est notamment le cas au niveau des nerfs olfactifs qui ont pour origine les neurones présents dans la cavité nasale. Ces neurones participent à la détection des odeurs et leurs axones contactent directement le système nerveux central au niveau des bulbes olfactifs en traversant la lame criblée de l’éthmoïde. Cette « voie olfactive » représente ainsi un site d’entrée privilégié de certains pathogènes vers le cerveau. La muqueuse olfactive, du fait de son positionnement à l’interface entre l’environnement et le système nerveux central, constitue donc une zone particulièrement sensible sur le plan immunologique. Si cette muqueuse est connue pour produire des composants antimicrobiens, les mécanismes cellulaires et moléculaires mobilisés dans le cadre d’infections par des pathogènes respiratoires restent peu décrits.Au cours de ma thèse, nous nous sommes tout d’abord focalisés sur l’interleukine 17c, connue comme puissant médiateur des réponses immunitaires innées épithéliales respiratoires et dont les récepteurs sont exprimés dans la muqueuse olfactive. Nous avons notamment pu montrer qu’elle était mobilisée in vivo dans un contexte mimant une infection virale et qu’elle favorisait le renouvellement épithélial ainsi que l’infiltration de cellules immunitaires. En voulant caractériser son action dans un contexte viral, nous avons été amenés à étudier les effets de deux virus respiratoires sur la muqueuse olfactive (le virus influenza et le virus respiratoire syncytial). Nous avons observé que les deux virus pouvaient infecter efficacement les neurones sensoriels olfactifs, mais avec une charge virale plus élevée pour influenza. A dose équivalente, le virus de la grippe provoque d'importants dégâts dans la muqueuse olfactive mais ne s’établit pas durablement dans la muqueuse, ce qui suggère que ce virus est éliminé très efficacement et rapidement. En nous focalisant sur les processus d'élimination des neurones sensoriels olfactifs infectés, nous avons identifié un nouveau mécanisme antiviral précoce basé sur l'élastase, une enzyme précédemment décrite comme sécrétée par les neutrophiles, principaux acteurs du système immunitaire inné.Dans l’ensemble, ces travaux de thèse mettent en lumière les défenses immunitaires présentes dans la cavité nasale contre les virus respiratoires et apportent de nouvelles perspectives dans le contrôle des virus infectant le système nerveux central par la voie olfactive
The central nervous system is sheltered from the environment thanks to cranial bones and the blood brain barrier. Some parts of these barriers are weaker, especially around olfactory nerves originating from olfactory sensory neurons in the nasal cavity. These neurons detect odorants and their axons cross the cribriform plate to project directly into the brain at the level of the olfactory bulbs. The cribriform plate is a thin and perforated area of the cranial bones allowing the crossing of the olfactory nerves. This “olfactory pathway” constitutes a privileged entry site for viruses toward the central nervous system. Hence, the olfactory mucosa represents a particularly sensitive area for the immune system. While the olfactory mucosa is known to produce various anti-microbial compounds, the described molecular and cellular mechanism of immune system defenses against viruses remains sparse.The interleukin 17c (IL-17c) is known as an innate immunity response actor in the respiratory epithelium. While its receptors are expressed in the olfactory mucosa, its role in this tissue was unknown. We found that IL-17c is involved in olfactory mucosa responses to Poly(I:C) mimicking virus presence. We observed that nasal instillation of IL-17c accelerated the olfactory mucosa turn-over and induced its infiltration by immune cells. In attempt to characterize the role of IL-17c in a real viral context, we started to focus on the impact of two viruses of the respiratory tract: influenza and the respiratory syncytial virus. We observed that both viruses could effectively infect olfactory sensory neurons but with a higher virus load for influenza. Indeed, at similar doses, influenza induced important damages in the olfactory mucosa but was not present, indicating that influenza virus is very effectively and rapidly eliminated from the olfactory mucosa. By focusing on the elimination processes of infected olfactory sensory neurons, we identified a novel early anti-viral mechanism based on elastase, an enzyme previously described as secreted by neutrophils, main actors of the innate immunity system.Overall, my PhD results provide new insights on the immune defenses present in the olfactory mucosa against respiratory viruses and could bring new perspectives in the control of virus infecting the central nervous system

Face à une concurrence de plus en plus vive, les professionnels se soucient de plus en plus de l'ambiance de leurs magasins. Leur intérêt se porte aujourd'hui sur la dimension olfactive de l'atmosphère. Notre objectif fut de vérifier l'intérêt de cette variable et de tester l'influence que pouvait avoir la diffusion de senteurs d'ambiance sur les réponses émotionnelles, cognitives et comportementales de clientes interrogées au sein d'un magasin de prêt-à-porter féminin. Dans une première partie, nous avons réalisé une revue de littérature qui nous a permis de revenir sur le concept de lieu. Nous avons proposé d'en distinguer trois types ainsi que trois atmosphères. Ensuite, nous avons examiné les contributions de la psychologie environnementale à l'étude de la relation individu-environnement. Enfin, nous avons confronté les mythes généralement associés aux odeurs aux connaissances scientifiques acquises sur leur perception et leur influence. La seconde partie de notre travail fut consacrée au test de l'impact de la diffusion de senteurs d'ambiance au sein d'un magasin de prêt-à-porter féminin. Nous avons adopté une approche positive basée sur le paradigme SOR. Une première étude, menée auprès de 253 femmes, a permis de sélectionner deux senteurs. Ensuite, les effets de la diffusion de ces deux senteurs furent examinés au cours d'une étude portant sur un échantillon de 230 femmes. Afin de tester les hypothèses formulées, nous avons eu recours à des analyses de variance ainsi qu'à des méthodes avancées (équations structurelles et tests non paramétriques). Cela nous a permis de vérifier l'influence que pouvait avoir la diffusion de senteurs sur les réponses affectives (dimension plaisir), cognitives (évaluation du temps écoulé...) et comportementales (temps de présence). Enfin, nous avons étudié la médiation des réponses affectives et la modération des variables âge et fumeur (équations structurelles). Enfin, différentes recommandations managériales ont été faites.

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One of the human senses that has several aspects get to be elucidated is the olfactory sense. Therefore, many scientists have been studying this sense in order to better understand how does the information processing happens until the brain recognize it. There were lots of theories regarding olfactory system functioning, in which its authors try to explain how the reception, the analysis and the odor detection occur. Many people still use their own noses as a working tool. In this kind of job, people are trained to inhale and detect different odors. It is considered as an exhausting and risky job for those professional that, for example, could inhale toxics gases. In order to solve this problem, many systems that try to simulate a biological nose were developed. These systems are known as artificial noses. An artificial nose is an equipment composed of sensors and a pattern recognition system. The sensors are responsible for detecting odor signs from the external environment. The pattern recognition system is used to classify the signs sent by sensors and to provide a result from these signs.In the present work, artificial neural network techniques were used for the patternrecognition process, once these techniques are non-parametric and usually nonlinear. The usage of artificial neural networks as an odor recognition system has been quite advantageous. These networks are capable of working with non-linear data and also have an adaptation capability, they are tolerant to errors and noise, and have parallel processing. MLP, RBF e PNN were used in the development of an odor recognizing system based on a biologic system model and its results were compared, using the Wilcoxon test on the respective network models without the adaptation to the biologic model.
Um dos sentidos humanos que apresenta vários aspectos que ainda precisam ser elucidados é o sentido do olfato. Para isto muitos pesquisadores vêm estudando este sentido para melhor entender como ocorre o processamento das informações até a etapa de reconhecimento feita pelo cérebro. Desses estudos muitas foram as teorias propostas sobre o funcionamento do sistema olfativo, onde seus autores procuram esclarecer como ocorre a recepção, análise e detecção do odor. Muitas pessoas ainda têm como ferramenta de trabalho seus próprios narizes. Nesse tipo de trabalho pessoas são treinadas para inalar e detectar odores. Esse trabalho é considerado exaustivo e de risco para o profissional que, por exemplo, pode vir a inalar gases tóxicos. Para solucionar esse problema foram criados sistemas que simulam o nariz biológico. Esses sistemas são chamados de narizes artificiais. O nariz artificial é um equipamento formado por sensores e um sistema de reconhecimento de padrões. Os sensores são responsáveis por captar do meioexterno os sinais de odor. O sistema de reconhecimento de padrões é utilizado para classificar os sinais enviados pelos sensores e apresentar um resultado. No presente trabalho, foram utilizadas as técnicas de redes neurais artificiais para o reconhecimento de padrões. Pois essas técnicas são não-paramétricas e geralmente são não-lineares. A utilização de redes neurais artificiais como sistema de reconhecimento de odor tem sido bastante vantajosa. Elas têm a capacidade de trabalhar com dados não-lineares, possuem capacidade de adaptação, são tolerantes a erros e a ruídos e também possuem processamento paralelo. Foram utilizadas as redes MLP, RBF e PNN para o desenvolvimento de um sistema de reconhecimento de odor baseado em um modelo do sistema olfativo biológico e seus resultados foram comparados, utilizando o teste de Wilcoxon, com os respectivos modelos de redes sem a adaptação ao modelo biológico.

INTRODUÇÃO: O diagnóstico da doença de Parkinson (DP) pode ser um desafio, principalmente nas fases precoces da doença. O diagnóstico acurado desta condição requer mais que a avaliação clínica isolada. A Tomografia computadorizada do crânio de fóton único (SPECT) e a ultrassonografia transcraniana (USTC) podem ser úteis na diferenciação entre a DP e as síndromes parkinsonianas atípicas ou entre a DP e o tremor essencial. O presente estudo objetivou investigar a acurácia da USTC combinada com o teste de olfação Sniffin\' Sticks (SST-16) para diferenciar pacientes com DP de controles saudáveis e comparar com a acurácia do SPECT com 99mTc- TRODAT-1 (TRODAT). MÉTODOS: Trata-se de um estudo transversal que incluiu pacientes com DP segundo critérios do United Kingdom Parkinson\'s disease Society e um grupo controle de indivíduos saudáveis pareados para idade e gênero. Os pacientes foram examinados por um especialista em distúrbios do movimento e submetidos a SPECT encefálico com TRODAT, USTC e SST-16. Curvas Receiver Operating Characteristic (ROC) foram obtidas para definir os pontos de corte dos métodos avaliados para detecção de DP. RESULTADOS: Vinte indivíduos com DP (13 homens e 7 mulheres) e 9 participantes saudáveis foram admitidos no estudo. A idade mediana de início dos sintomas foi de 56,5 anos e a mediana do tempo de duração da doença foi de 5 anos. Maior área de ecogênica da substância negra (SN) foi observada no grupo com DP (p=0,013). Área ecogênica da SN de 0,22 cm2 foi definida pela curva ROC para detecção de DP, com acurácia de 79%. O ponto de corte do potencial de ligação do TRODAT no striatum foi 0,90, com acurácia de 99% para o diagnóstico de DP. Escore do SST-16 maior ou igual a 10 pontos foi o ponto de corte para detecção de DP, com acurácia de 85,8%. A combinação da USTC com teste da olfação levou à acurácia de 95% para detecção de DP. CONCLUSÃO: A combinação da USTC com SST-16 eleva a capacidade de ! detecção da DP. A acurácia da USTC combinada ao SST-16 para identificar pacientes com DP idiopática aproximou-se da acurácia do SPECT com TRODAT
INTRODUCTION: Diagnosing Parkinson\'s disease (PD) can be challenging, especially in the early stages of the disease. An accurate diagnosis requires more than clinical findings alone. Brain single-photon emission computed tomography (SPECT) and transcranial sonography (TCS) are helpful for diagnosing PD and differentiating it from atypical parkinsonian syndromes as well as essential tremor. This study aimed to investigate the accuracy of TCS combined with the Sniffin\' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex-matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, Striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p=0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% accuracy for the diagnosis of PD. SST-16 values equal or greater than 10 points showed a 85.8% accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the accuracy to 95% for PD diagnosis. CONCLUSION: Combined assessment of SST-16 and TCS are reliable and highly accurate for distinguishing PD patients from healthy controls. The accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT

Ce doctorat a pour objectif de contribuer à une meilleure compréhension du lien, plusieurs fois démontré, entre odeurs et couleurs. Il s’organise en 4 parties correspondant à 4 grandes études réalisées dans différents pays, la France, le Liban et Taiwan, ainsi que dans différentes régions au sein d'un même pays (Liban urbain, Liban rural). La première étude effectuée dans les trois pays avait pour objectif de démontrer l’impact de la culture sur la construction du lien odeurs – couleurs. Les résultats obtenus ont mis en évidence un effet significatif du lieu de résidence des participants sur la construction du lien mais aussi du rôle prépondérant de la « fonction de l'odeur » (alimentaire, cosmétique, industrielle, …). La seconde étude interculturelle entre la France et le Liban s’est intéressée plus spécifiquement à la méthodologie employée pour réaliser les tests odeurs – couleurs. En effet, dans la littérature, deux types de procédures sont généralement employées soit la présentation de couleurs physiques que le participant peut regarder soit l’absence de présentation de couleurs physiques et l’utilisation de noms de teintes (bleu, vert, rouge, …). La comparaison de ces deux méthodes a mis en évidence un effet de la procédure tout aussi important que celui de la culture et de la fonction de l'odeur sur l'association odeur-couleur. Les données ont aussi mis en évidence un réel pouvoir d’évocation olfactive des couleurs. Pour mieux, comprendre ce phénomène, nous avons réalisé une étude en IRMf. Cette troisième étude utilisant l'IRMf a montré que le pouvoir d’évocation olfactive d’arrangements abstraits de couleurs était différent de celui obtenu à partir de représentations visuelles figuratives colorées. Les processus cognitifs mis en œuvre lors d’une évocation olfactive à partir de couleurs sont plus complexes et multimodaux impliquant des processus olfactifs, émotionnels, visio-spatial, du langage ainsi que la mémoire. La dernière partie de ce doctorat s’est intéressé à mieux comprendre comment les processus émotionnels mis en évidence par IRMf pouvaient interférer avec la construction du lien odeurs – couleurs. L’étude a été réalisée en France ainsi que dans deux régions, rurale et urbaine, du Liban. Les résultats ont montré que l'affect associé à une odeur influençait le lien odeurs-couleurs mais surtout, que le choix préférentiel de certains affects était lié à la situation socio-économique et culturel du participant. Cette thèse est donc une contribution à une meilleure compréhension du lien qui unit odeurs et couleurs. Elle en a démontré la complexité avec un effet avéré de la fonction de l’odeur dans le pays, de la méthodologie employée ainsi que du lieu de résidence et du niveau socio-culturel du participant. Elle souligne cependant la nécessité d’une approche multidisciplinaire pour en comprendre encore plus précisément l’ensemble des rouages
This doctorate aims to contribute to a better understanding of the link, several times demonstrated, between odors and colors. It is organized in 4 parts corresponding to 4 major studies carried out in different countries, France, Lebanon and Taiwan, as well as in different regions within the same country (urban Lebanon, rural Lebanon). The first study carried out in the three countries aimed at demonstrating the impact of culture on the construction of the odor-color link. The results obtained revealed a significant effect of the participants' place of residence on the construction of the link but also the predominant role of the "function of the odor" (food, cosmetics, industrial ...). The second intercultural study between France and Lebanon focused more specifically on the methodology used to carry out odor - color tests. Indeed, in the literature, two types of procedures are generally used: presentation of physical colors that the participant can see or absence of presentation of physical colors and the use of color names (blue, green, red, ...). The comparison of these two methods revealed an equally important effect between the procedure, the culture and the function of the odor on the odor-color association. The data also revealed that colors have the capacity of olfactory evocation. To better understand this phenomenon, we performed an fMRI study. This third study using fMRI showed that the olfactory evocation power of abstract color arrangements was different from that obtained from colored figurative visual representations. The cognitive processes involved in an olfactory evocation from colors arrangement, is more complex and multimodal involving olfactory, emotional, visio-spatial, language and memory processes. The final part of this Ph.D. examined how emotional evidenced by fMRI could interfere with the construction of the odor - color link. The study was carried out in France as well as in two rural and urban areas of Lebanon. The results showed that the affect associated with an odor influenced the odor-color link, but above all, that the preferential choice of certain affects was linked to the socioeconomic and cultural situation of the participant. This thesis is therefore a contribution to a better understanding of the link between odors and colors. It has demonstrated its complexity with a proven effect of the odor function in the country, the methodology used and the place of residence and socio-cultural level of the participant. However, it stresses the need for a multidisciplinary approach to understand even more precisely the whole workings

Objectives The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function. Materials & methods A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects. Results Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III. Conclusions Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

Research Doctorate - Doctor of Philosophy (PhD)
ABSTRACT: Purpose (Aims): To determine 1) if there is an association of the Olfactory ‘Stress’ Test (OST) or conventional olfaction with cognition; 2) if baseline olfactory scores and the OST predict a change in cognition (CC); 3) if the relationship between cognition and the OST (or conventional olfaction) is influenced by brain reserve or cognitive reserve measures; and 4) if performance on the OST (or conventional olfaction) is associated with subjective memory complaints. Methods: The OST study included two phases: I (baseline, mixed clinical trial and cross-sectional study) including 295 community-dwelling elderly Australians and II (follow-up on average of 4.018 years later). Olfaction was assessed using the University Of Pennsylvania Smell Identification Test (UPSIT). The OST result (atropine effect, AE) is the score on the second 20-odor set of the UPSIT (post-intranasal atropine) minus that on the first 20-odor set (pre-intranasal atropine (preup)). Conventional olfaction included preup and hyposmia rating scale (HRS). Cognitive measures included the Audio Recorded Cognitive Screen and Standardized Mini-Mental Status Examination; CC is (phase II minus phase I) cognitive scores. Main algorithms and/or statistical methods used: Objectives 1 and 2 – linear and logistic regression, propensity score analysis; objective 3 – linear regression; and objective 4 – linear and logistic regression. Other methods and/or algorithms used include K-Means clustering, K-Nearest Neighbor classification, naïve Bayes and decision tree analysis. Results: The higher the preup, but the lower the AE and HRS, the higher the cognition was. AE < 0 (cholin = 0) was associated with higher phase I and II OST study cognitive scores than AE ≥ 0 (cholin = 1). Education level modifies the association of cholin, preup-75 and modified UPSIT classes (MC) with cognition. Clusters of AE or preup with ARCS scores have stronger associations with cognition than either AE or preup alone. Preup and cholin are associated with a single question history of memory loss (SML). History of depression modifies the association of cholin with SML. Conclusion: Conventional olfaction and cholin are predictors of CC. The OST (through cholin) is a potential biomarker for underlying AD, cholinergic neurodegeneration and SML pathology.

A influência dos estímulos sensoriais no comportamento do consumidor é uma vantagem de competição por parte das empresas. No que diz respeito ao Marketing Olfactivo é importante perceber se os consumidores conseguem identificar o aroma ao qual estão expostos. Os estímulos olfactivos podem afectar a atitude do consumidor e a opinião que estes têm em relação ao espaço em questão. O objectivo principal deste trabalho é criar uma identidade olfactiva para o Hotel Moliceiro. Com o objectivo de confirmar a afirmação acima mencionada, desenvolveu-se um estudo em duas fases. Primeiro, realizou-se uma revisão da literatura sobre o que é o Marketing Sensorial e mais concretamente o Marketing Olfactivo e quais as suas vantagens e desvantagens. Segundo, procedeu-se à aromatização do Hotel Moliceiro, para perceber se os clientes percepcionavam o aroma e qual a avaliação que estes faziam ao espaço do Hotel, foi ainda desenvolvido um questionário aplicado junto dos clientes para recolher a opinião dos mesmos sobre o aroma. A recolha de dados decorreu nos dias 17, 18 e 19 de Abril, resultando numa amostra de 70 questionários. Através dos resultados obtidos percebeu-se que o aroma seleccionado é do agrado geral dos inquiridos e assim conseguiu criar-se uma identidade olfactiva potencial interesse para o Hotel Moliceiro. Percebeu-se ainda que o género não tem influência directa na avaliação do aroma, mas, por outro lado, o facto de ser fumador tem influência num dos campos da avaliação do aroma.

O presente estudo aborda o tema de marketing sensorial e visa conhecer o impacto do estímulo olfactivo - de cheiro a carro novo - no curso de uma experiência de test drive de um Fiat 500S. Os principais objectivos são a) identificar as percepções sobre a marca Fiat e, mais concretamente, do modelo 500, b) perceber as motivações subjacentes à compra de um carro novo e de um Fiat 500, c) perceber o efeito do estímulo olfactivo na avaliação do carro e na propensão para a compra do mesmo, e d) identificar o impacto do estímulo sensorial no comportamento de condução, em termos de velocidade máxima atingida e consumos de combustível da viatura. Para atingir os objectivos propostos, realizou-se um estudo exploratório com recurso a entrevistas semi-estruturadas a dezasseis potenciais compradores do modelo Fiat 500, com o objectivo de conhecer as suas motivações de compra e perceções do produto. Igualmente, os participantes foram divididos em dois grupos - grupo de controlo (sem estímulo olfactivo) e grupo experimental (com o característico cheiro a carro novo, no interior da viatura) - de forma a perceber o impacto deste estímulo na avaliação do produto e comportamento durante a condução. O estudo realizado sugere que o estímulo olfactivo, de cheiro a carro novo, tem impacto sobre o comportamento do potencial comprador e na intenção de compra da viatura.
The present study addresses the topic of sensory marketing, and aims to learn about the impact of an olfactory stimulus - the typical scent of a brand new car - within the course of a test drive experience of a Fiat 500S. The main objectives are to a) identify the perceptions of the brand Fiat, and more concretely, of the model 500, b) learn about the motivations to buying a new car and a Fiat 500, c) study the effect of an olfactory stimulus on the car's evaluation and on the propensity to purchase it, and d) to identify the impact of a sensorial stimulus on the driving behavior, in terms of maximum speed reached and fuel consumption.To achieve the proposed goals, it was carried out an exploratory study using semi-structured interviews done to sixteen potential buyers of the Fiat 500, in order to learn about their motivations of purchase and perceptions of the product. Likewise, the participants were divided into two groups - the control group (without the olfactory stimulus) and the experimental group (with the characteristic scent of a brand new car, inside the vehicle) - in order to acknowledge the impact that this stimulus has on the evaluation of the product and driving behavior. The present study suggests that the olfactory stimulus, in this case the scent of a new car, has impact on the behavior of potential buyers, as well as on the purchase intention of the car.

Tese de doutoramento em Ciências da Saúde, no ramo de Medicina, apresentada à Faculdade de Medicina da Universidade de Coimbra
Usher syndrome (USH) is an autosomal recessive disorder characterized by the association of sensorineural hearing loss (SNHL), visual loss due to retinitis pigmentosa (RP) and in some cases, vestibular dysfunction. USH is divided into three subtypes according to the disease severity and progression. Type I (USH1) is characterized by profound congenital SNHL, prepuberal onset of RP, and vestibular dysfunction. Type II (USH2) is characterized by moderate to profound (sloping pattern) congenital SNHL, later onset of RP and normal vestibular function. Type III (USH3) displays post lingual, progressive SNHL, variable vestibular dysfunction, and variable onset of RP. A certain degree of overlapping and atypical cases coexist. Until now, 10 causative genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2 in USH1; USH2A, GPR98, DFNB31 in USH2 and CLRN1 in USH3) and three additional loci have been identified. In addition, three other genes have been associated with USH: PDZD7, HARS and CEP250. A significant genetic heterogeneity is also found. Genotype-phenotype correlation is a challenging task both for clinicians and geneticists. This is due to the rarity of the disease character and its notorious phenotypic and genotypic heterogeneity. Second, patients with the same mutation do not have the same natural history. Finally, there are no established sensitive biomarkers for early diagnostics and/or disease progression. We aimed to study a new cohort of USH patients using state-of-the-art audiovestibular and ophthalmological clinical examination in parallel with molecular analyses, with the intention to improve early diagnosis and genotype-phenotype correlations. Deep phenotyping of other senses like olfaction may uncover novel biomarkers for diagnosis and prognosis. A new Portuguese cohort of 102 USH patients was established. USH prevalence is 9.8 per 100 000 habitants. USH type I (USH1) patients represent 36% and USH type II (USH2) 62% of total USH cases, meaning a USH1 prevalence of 3.5, USH2 of 6.1, and USH3 of 0.2 per 100 000 habitants. The targeted next generation sequencing based molecular diagnosis oriented by patient clinical information presented a detection rate of 90.2% of mutations in the analyzed subset. MYO7A was responsible for 62% of USH1 cases and USH2A for 72% of UHS2 cases. Atypical genotype-phenotype correlations were observed in 10% of our cases, being particularly relevant in PCDH15, CDH23 and USH2A patients. Recent evidence indicates that USH may belong to an emerging class of sensory ciliopathies. Genetics, biochemistry and proteomic approaches have demonstrated that USH proteins are organized in networks in both the eye and the inner ear. Because olfaction has very recently been implicated in sensory ciliopathies, it is expectable that it is also implicated in USH. Nevertheless, very few conflicting papers studied olfaction in USH. Olfaction plays an important role in our health, safety and quality of life, but there was no previous olfactory test adapted and validated for the Portuguese population. Sniffin´ Sticks olfactory test is the most widely studied test in Europe. We have cross-culturally adapted and validated it for the Portuguese population (SnSt-pt) based on 4 experiments: In Experiment 1, we assessed the familiarity of the odors presented and seven descriptors of the original test were adapted to the Portuguese context. In experiment 2, we administered the SnSt-pt to 203 healthy participants. Our third experiment confirmed the validity of the SnSt-pt in discriminating healthy controls from patients with olfactory dysfunction. In Experiment 4, the test-retest reliability for both the composite score (r71=0.86) and the identification test (r71=0.62) was established (p<0.001) This study provides normative data for the SnSt-pt, showing good validity and reliability and effectively distinguishing patients from healthy controls with high sensitivity and specificity. The cut-off score is 31.75 (29.45 for men and 34.35 for women), which allows a direct comparison with other European populations in many different studies and diseases. Olfaction is not well studied in USH patients. In fact, only a few controversial papers with some methodological questionable points addressed it. In light of this controversy and perceiving the importance of studying olfaction in USH patients, we have prospectively evaluated 65 USH patients and 65 normal age- sex – smoking status matched subjects using the SnSt-pt after detailed rhinological evaluation. USH1 showed significantly higher scores than USH2 and a much faster decline in their olfactory function than what happens in healthy controls and USH2. Our study revealed significantly better olfaction scores in USH1 younger patients. Olfactory testing represents an attractive tool for USH subtype classification and pre diagnostic screening due to the low cost and minimally invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of USH. Future multicenter studies integrated with olfactory receptor genotyping are likely to allow a better discrimination between patients with USH.
A Síndrome de Usher (USH) é uma doença autossómica recessiva onde se associa uma surdez neurossensorial, défice visual devido a retinopatia pigmentar (RP) e, em alguns casos, disfunção vestibular. A USH é dividida clinicamente em três tipos de acordo com a gravidade e progressão da surdez, e a presença ou não de alterações vestibulares. O tipo I (USH1) apresenta surdez congénita profunda, RP precoce e alterações vestibulares. O tipo II (USH2) apresenta uma surdez congénita moderada a severa, RP mais tardia e função vestibular normal. O tipo III (USH3) apresenta uma surdez progressiva, função vestibular e início de RP variáveis. Encontram-se descritas mutações em 10 genes relacionados com a USH (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2 no USH1; USH2A, GPR98, DFNB31 no USH2 e CLRN1 no USH3). Outros três loci estão identificados, e três genes adicionais foram associados a USH (PDZD7, HARS e CEP250), A relação genótipo – fenótipo na USH constitui um desafio importante quer para o médico quer para o geneticista. Trata-se de uma doença rara com uma grande heterogeneidade clinica e genética em que doentes com a mesma mutação não apresentam a mesma história natural da doença. A relação genótipo-fenótipo é ainda dificultada pela ausência de biomarcadores sensíveis e adequados ao seu diagnóstico ou avaliação prognóstica. Com esta tese, ao estabelecer uma base de dados de doentes com USH através de um estudo clinico audiovestibular e oftalmológico e análise genética detalhadas, procura-se melhorar o diagnóstico precoce, estabelecer novas relações genótipo-fenótipo e/ou consolidar relações já estabelecidas. A fenotipagem de outros sentidos como o olfacto pode eventualmente revelar novas ferramentas diagnósticas ou prognósticas da USH. Após o recrutamento prospetivo de 102 doentes com USH, a prevalência foi estabelecida em 9.8 casos por 100 000 habitantes. A USH1 representa 36% e USH2 62% do total, correspondendo a 3.5 USH1, 6.1 USH2 e 0.2 USH3 por 100 000 habitantes. A sequenciação genética de nova geração orientada pela clinica permitiu uma taxa de deteção de mutações de 90.2%. O gene MYO7A foi responsável por 62% dos casos de USH1 e o USH2A por 72% dos casos USH2. Observaram-se formas atípicas em 10% dos doentes, em particular naqueles com mutações em PCDH15, CDH23 e USH2A. O olfacto tem um papel relevante na saúde, segurança e qualidade de vida da população, mas não se encontrava ainda descrito um teste de olfacto adaptado culturalmente à população Portuguesa. O teste de olfacto mais estudado na Europa é o Sniffin´ Sticks. Nesta tese procedeu-se à sua adaptação e validação para a população portuguesa em quatro experiências: na primeira avaliou-se a familiaridade de cada odor e foram adaptados 7 descritores a partir da versão original. Num segundo passo, a versão portuguesa do Sniffin` Sticks (SnSt-pt) foi aplicada a 203 participantes saudáveis. Indivíduos mais idosos, género masculino e fumadores ativos obtiveram piores resultados, tal como na versão original. A terceira experiência confirmou que o SnSt-pt permite, efetivamente, discriminar doentes anósmicos de controlos saudáveis. A última experiência avaliou a relação entre o teste e re-teste SnSt-pt (r=0.86, p<0.001). Apresentam-se, ainda, os dados normativos do SnSt-pt para a população portuguesa, verificando-se uma adaptação válida que distingue os doentes com disfunção olfactiva de controlos saudáveis com uma alta sensibilidade e especificidade. Alguns estudos recentes sugerem que a USH pode pertencer a uma nova classe de ciliopatias sensoriais. De facto, abordagens genéticas, bioquímicas e proteómicas demonstraram que as proteínas de USH se encontram organizadas em rede no olho e no ouvido interno. O olfacto tem sido cada vez mais envolvido em ciliopatias sensoriais, pelo que é assim expectável que este também se encontre alterado nos doentes com USH. Os escassos estudos publicados sobre o envolvimento do olfacto na USH demonstram resultados dispares e questões metodológicas discutíveis. Como um contributo adicional para o estudo multissensorial da doença, foram efetuados estudos olfactivos em 65 doentes com USH e 65 controlos emparelhados por idade, sexo e hábitos tabágicos. Os resultados indicam que os doentes com USH1 jovens apresentam melhores scores que os controlos saudáveis e do que os doentes com USH2. A perda olfactiva não relacionada com a idade foi muito significativa nos doentes com USH1, ao contrário do que foi observado para os USH2. Estes dados indicam que o teste olfactivo pode constituir uma ferramenta útil para a classificação clínica da USH e como teste de rastreio prático devido ao seu baixo custo e à natureza não invasiva da avaliação. Com base nos resultados apresentados nesta tese sugere-se que as alterações do olfacto sejam consideradas entre as manifestações clínicas da USH. Estudos multicêntricos futuros que permitam avaliar a influência genética de receptores olfactivos em USH poderão facilitar uma melhor discriminação entre doentes com diferentes tipos de USH.
FCT - E-Rare4/0001/2012E