A proteína Cpn60 faz parte de um grupo de proteínas altamente conservadas que estão envolvidas em funções celulares essenciais. camundongos BALB\\c foram imunizados com 5 ou 10 µg da proteína recombinante (Cpn60r) sozinha ou adicionada à vacina DTP sem hidróxido de alumínio (NADTP). A vacina DTP do Instituto Butantan (DTP) foi usada como controle. Foi avaliada a produção de citocinas por células esplênicas após reestímulo in vitro com a Cpn60r. Os animais foram desafiados após o protocolo de imunização. A Cpn60r sozinha ou misturada à vacina NADTP foi capaz de induzir níveis de anticorpos contra pertussis mais altos do que os induzidos pela DTP. Os níveis de IgG1 e IgG2a foram similares para todos os grupos. Pôde-se observar a produção de de IL-6 e IFN-&#947 nos grupos imunizados com Cpn60r. Os grupos imunizados com Cpn60r+NADTP apresentaram um índice de proteção entre 60 e 80% contra o desafio pela bactéria virulenta, semelhante ao grupo imunizado com DTP. A proteína Cpn60r é bastante promissora não somente como imunógeno, mas também como adjuvante. / The Cpn60 protein is a member of a group of higly conserved proteins linked to essencial cell functions. The Cpn60 was cloned, expressed and its immune response has been evaluated. BALB\\c mice were immunized with 5 or 10 µg of the recombinant protein (Cpn60r) alone or mixed with DPT vaccine without aluminum hidroxyde (NADPT). The DPT vaccine from Instituto Butantan was used as control. We evaluated the cytokines production by spleen cells after they have been reestimulated in vitro with Cpn60r. The animals were challenged after the immunization protocol. The Cpn60r alone or mixed with NADPT vaccine was able to induce higher antibodies levels than DPT. IgG1 and IgG2a levels were similar in all groups. We could detect levels of IL-6 and IFN-&#947 on groups immunized with Cpn60r. The groups immunized with Cpn60r+NADTP showed a 60 and 80% protection rate against the challenge with the live bacteria, similar to the group immunized with DPT. These results show the immune response of the recombinant protein that could be included in immunization protocols for pertussis.

The main objective of this research was to exploit the interrelations between the rheological behavior and nano-microstructure of complex fluids in solving two state-of-the-art problems, one in the field of biomedical engineering: controlling the amount and characteristics of bioaerosol droplets generated during coughing, and the other in the bitumen-heavy oil industry: characterizing the nano-microstructure of asphaltene particles in bitumen and heavy oil from their rheological behavior. For the first problem, effect of viscoelastic and surface properties of artificial mucus simulant gels on the size distribution and amount of airborne bioaerosol droplets generated during simulated coughing were investigated. The results revealed that suppressing the generation of bioaerosol droplets and/or reducing the number of emitted droplets to a minimum during coughing are practically achievable through modulation of mucus viscoelastic properties. While variation of surface tension did not show any change in the droplet size distribution, an increase in particle size was observed as the samples changed from elastic solid type to viscoelastic type to viscous fluid type samples. This knowledge will help in the development of a new class of drugs being developed at the University of Alberta, aimed at controlling the transmission of airborne epidemic diseases by modifying the viscoelastic properties of mucus. For the second problem, studies of viscoelastic behavior of Athabasca bitumen (Alberta) and Maya crude (Mexico) oil samples, along with their Nano-filtered and chemically separated-plus-reconstituted samples were performed. The results revealed that the rheological behaviors of the bitumen-heavy oil samples are governed by their multiphase nature. The rheological behavior of all feeds, permeates and retentate samples followed a single master curve over the entire temperature interval, consistent with that of a slurry comprising a Newtonian liquid plus a dispersed solid comprising non-interacting hard spheres. The behavior of asphaltenes in the reconstituted samples, however, was found to be significantly different from that in nanofiltered samples. The information about the characteristics and behaviors of asphaltenes obtained in this study will help better understand the asphaltene structures, and support the effort to determine solutions for numerous asphaltene-related industrial problems. In the long run, this knowledge will help to create more efficient extraction and upgrading processes for bitumen and heavy oils. / Thermo Fluids

No description available.

Ο βήχας είναι ένα κοινό σύμπτωμα σε πολλές ασθένειες του αναπνευστικού συστήματος. Αν και λειτουργεί ως προστατευτικός μηχανισμός απομάκρυνσης εκκρίσεων από την αναπνευστική οδό, η αυξημένη συχνότητα και έντασή του μπορεί να έχουν επίδραση στην ποιότητα ζωής του ασθενούς. Είναι το βασικότερο σύμπτωμα για το οποίο κάποιος επισκέπτεται τον γιατρό. Η σωστή εκτίμησή του είναι απαραίτητη τόσο για τον προσδιορισμό της αποτελεσματικότητας της θεραπείας αλλά και για την δοκιμή νέων θεραπειών και τη μελέτη των μηχανισμών του. Μέχρι στιγμής η διάγνωσή του βασίζεται σε υποκειμενικές καταγραφές, απλώς ζητώντας από τον ασθενή την εκτίμησή του για την ένταση, τη διάρκεια και τη συχνότητά του. Ένα σύστημα αυτόματης ανίχνευσης του σήματος του βήχα θα επέτρεπε την επικύρωση της παρουσίας και της συχνότητας του βήχα καθώς και την αποτελεσματικότητα της αγωγής. Τα συστήματα καταγραφής του βήχα δεν είναι καινούρια διαδικασία. Η πρώτη καταγραφή έγινε τη δεκαετία του '60 σε νοσηλευόμενους ασθενείς με τη χρήση μαγνητοφώνων και με χειροκίνητη καταγραφή των γεγονότων του βήχα. Στη συνέχεια με την εξέλιξη της τεχνολογίας κατασκευάστηκαν φορητές συσκευές που βασίστηκαν στην ταυτόχρονη καταγραφή ήχου και ηλεκτρομυογραφήματος (EMG σήματα, ανίχνευση κίνησης του θώρακα) για να ανιχνευθούν τα γεγονότα του βήχα όπου ακόμα τα σήματα έπρεπε να καταγραφούν και να μετρηθούν χειροκίνητα. Με τις παραπέρα ανακαλύψεις στις τεχνικές ψηφιακής καταγραφής, συμπίεσης και αποθήκευσης η διαδικασία αναγνώρισης και καταγραφής του βήχα μπορεί να αυτοματοποιηθεί με τη χρήση κατάλληλων αλγορίθμων. Στην εργασία αυτή κατασκευάζεται ένα ενσωματωμένο σύστημα καταγραφής, αποθήκευσης και επεξεργασίας του σήματος του βήχα. Για την επεξεργασία του αναπτύσσεται μια βασική μέθοδος βασισμένη την ενέργειά του. Στο πρώτο κεφάλαιο, γίνεται αναφορά στα χαρακτηριστικά του ηχητικού σήματος και παρατίθενται τα βασικά στάδια της ανάλυσής του. Στο δεύτερο, δίνεται ο ορισμός του βήχα, οι αιτίες που τον προκαλούν και η φυσιολογία του. Στη συνέχεια, παρουσιάζονται μέθοδοι για την ανίχνευσή του. Στο τρίτο κεφάλαιο, αναφέρονται οι βασικές έννοιες των μικροελεγκτών και παρατίθενται τα βασικά χαρακτηριστικά του μικροεπεξεργαστή ARM7TDMI, του μικροελεγκτή ADuC 7026 και της αναπτυξιακής πλατφόρμας μVision της Keil που χρησιμοποιήσαμε για την ανάπτυξη της εφαρμογής μας. Στο τελευταίο κεφάλαιο, παρουσιάζονται κάποιες λειτουργίες προγραμματισμού και δυνατότητες του μικροελεγκτή που χρησιμοποιούνται στην παρούσα εργασία. Στη συνέχεια αναπτύσσεται η εφαρμογή για την ανίχνευση του σήματος του βήχα. Στα παραρτήματα, παρατίθενται παραδείγματα για τον βασικό προγραμματισμό του ADuC 7026 και των περιφερειακών του. / Cough is a common symptom in many diseases of the respiratory system. Although cough protects humans by removing secretions through respiratory track, its increased frequency and intensity may impact on patient’s quality of life. Besides, cough is the main symptom that makes people to visit doctor. Doctor’s accurate assessment is necessary for determining treatment according to each patient as well as the testing of new treatments and the comprehensive study of cough. So far, the diagnosis of cough is based on subjective factors such as patient’s assessment of its intensity, duration and frequency. An automatic detection system of the cough signal would allow to determine about the presence and frequency of cough and an effective treatment. The attempt to record cough is not a new process. The first recording to patients was made in 60’s by the use of tape recorders and by manually recording the symptoms of cough. As technology has evolved, portable device was created that was based on simultaneous recording of sound and electromyography (EMG signals, detection of the movement of chest) in order to detect the symptoms of cough. In that case, the recording was also made manually. With the evolution of digital recording, compression and storage, the recognition and recording of cough can be automated by using the appropriate algorithms. In that study, an embedded system is made in order to record, store and process the signal of cough. A basic method based on energy is developed for the process. In the fisrt chapter, the characteristics of sound signal and the key stages of the analysis are presented. In the second chapter, cough is defined, its causes and the clinical symptoms of cough are analyzed. Then, methods for its detection are specified. In the third chapter, the basic concepts of microcontrollers are given as well as the main characteristics of microprocessor ARM7TDMI and of microcontroller ADuC 7026 are presented and the platform μVision of Keil that we used for the development of the application is analyzed. In the final chapter, some programming functions and properties of microcontroller are presented and are used for the current study. Then, the application of detection of cough signal is developed. In annex, examples for the basic programming of ADuC 7026 and its peripherals are given.

INTRODUÇÃO: Uma epidemia de coqueluche ocorreu no Brasil, de 2011 a 2014. Isto levou à introdução da vacina tríplice acelular de adultos (dTpa) no calendário público de vacinação da gestante. Existem outras estratégias de vacinação envolvendo a dTpa, que poderiam complementar o controle da doença. Os objetivos deste estudo são descrever a epidemiologia da doença e avaliar custo-efetividade da vacinação de adultos com dTpa. MÉTODOS: 1) Uma revisão de literatura foi realizada nas bases MEDLINE, Excerpta Medica, CRD e Lilacs a partir de 2000. 2) Foi desenvolvido estudo observacional incluindo dados de vacinação e os casos notificados para o sistema de vigilância no Estado de São Paulo (ESP), de 2001 a 2015. 3) Foi realizado estudo descritivo dos pacientes com idade de 20 a <40 anos atendidos em um hospital do ESP entre 2010 e 2014, destacando-se a utilização de serviços de saúde. 4) Foi desenvolvido modelo dinâmico, para comparar a estratégia de vacinação com dTpa aos 20 anos de idade com o programa atual (vacinação com dT). Dados epidemiológicos e de custos foram retirados de sistemas de informação de saúde e da literatura nacional e internacional. Foram considerados como desfecho número de casos e mortes por coqueluche e anos de vida ganho (AVG). Considerouse a perspectiva do sistema de saúde, horizonte temporal de vinte anos e custos em Reais (R$) de 2015. Os resultados foram sumarizados em razão de custo-efetividade incremental (RCEI). Análises de sensibilidade uni e multivariadas foram realizadas. RESULTADOS: 1) Foram revisadas 28 avaliações econômicas de estratégias com dTpa. A vacinação de adolescentes e de adultos foram as mais avaliadas. A correção da subnotificação, uso de modelos dinâmicos, proteção de rebanho e altas coberturas vacinas influenciaram para o bom desempenho das estratégias. 2) Houve aumento de incidência da coqueluche entre 2011 e 2014 e queda da mesma em 2015, em todas as faixas etárias no ESP. Os lactentes foram os principais acometidos, mas a proporção de casos nessa faixa etária apresentou tendência de queda ao longo dos anos. A proporção de casos com idade de 1 a < 4, 5 a = 20 anos aumentou significativamente. Houve queda não significativa na proporção dos casos com idade < 2 meses de idade. 3) Entre 36 casos estudados no hospital, 33,3% passou por consulta prévia, 25,3% por consulta de retorno e 8,33% foram hospitalizados. Hemograma e radiografia de tórax foram os exames mais realizados. Não houve complicações ou óbito. 4) A vacinação de adultos com dTpa, com cobertura vacinal de 40% e efetividade de 75%, incluindo proteção de rebanho para os menores de um ano, evitaria 19.300 casos sintomáticos e 221 óbitos em 10 anos. A RCEI seria R$28.054,38/AVG. Na análise de sensibilidade, os resultados foram mais sensíveis a variações da incidência e à retirada da proteção de rebanho. CONCLUSÃO: O comportamento cíclico da doença é a principal causa da epidemia de coqueluche entre 2011 e 2014 e queda da incidência em 2015. A vacinação de adultos com dTpa não se mostrou custo-efetiva na realidade brasileira de 2015 / INTRODUCTION: A pertussis outbreak occurred in Brazil from 2011 to 2014. This led to the introduction of the maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) in the public immunization schedule. There are other vaccination strategies involving Tdap, which could complement the strategies of disease control. The objectives of this study are to describe the epidemiology of the disease and to evaluate cost-effectiveness of vaccination of adults with Tdap. METHODS: 1) A review was performed in the MEDLINE, Excerpta Medica, CRD and Lilacs databases from 2000. 2) Observational study was performed including vaccination data and the cases reported data from health surveillance datasets in the State of São Paulo from 2001 to 2015. 3) A descriptive study of patients aged 20 to < 40 years attended at a State of São Paulo hospital between 2010 and 2014 was performed, highlighting the use of health services.4) A dynamic model was developed to compare the vaccination strategy with Tdap at the age of 20 years with the current program (dT vaccination). Epidemiological and cost data were collected from health information systems and national and international studies. Number of cases and deaths by pertussis and life years saved (LYS) were considered as outcome. It was considered the health system perspective, a time horizon of 20 years and costs in 2015 Real (R$). The results were summarized by incremental costeffectiveness ration (ICER). Univariate and multivariate sensitivity analyzes were performed. RESULTS: 1) 28 economic evaluations of strategies with Tdap were reviewed. Vaccination of adolescents and adults were the most evaluated strategies. Underreporting correction, use of dynamic models, herd protection and high vaccination coverage influenced positively the performance of strategies. 2) The incidence of pertussis increased between 2011 and 2014, and its fall in 2015, among all age groups. Infants were the main affected, but the proportion of cases in this age group showed a downward trend over the years. The proportion of cases aged 1 to < 4, 5 to = 20 years increased significantly. There was a non-significant decrease in the proportion of cases aged < 2 months of age. 3) Among 36 cases studied in the hospital, 33.3% had a prior medical visit, 25.3% a return visit, and 8.33% were hospitalized. Blood count and chest X-ray were the most performed exams. There were no complications or death. 4) Vaccination of adults with Tdap, with 40% vaccine coverage and 75% effectiveness, including herd protection for children less than one year, would prevent 19,300 symptomatic cases and 221 deaths in 10 years. The ICER would be R$ 28,054.38/AVG. In the sensitivity analysis, the results were more sensitive to variations in incidence and withdrawal of herd protection. CONCLUSION: The cyclical pattern of the disease is the main cause of the pertussis epidemic between 2011 and 2014, and decreasing incidence in 2015. Adult vaccination with Tdap was not cost-effective in the 2015 Brazilian scenario

A coqueluche vem reemergindo enquanto importante problema de saúde pública em vários países do mundo, apesar das altas coberturas vacinais na infância. O objetivo geral deste estudo foi avaliar a morbimortalidade da coqueluche no Brasil e os objetivos específicos foram: estimar as taxas de mortalidade, incidência e letalidade anuais, geral e por faixa etária, por unidade da federação e regiões do país; caracterizar a sazonalidade da doença; estimar as taxas de hospitalização anuais por faixa etária e verificar as características clínicas, histórico de contato e vacinação prévia dos casos notificados da doença. Métodos: estudo descritivo, baseado nos casos de coqueluche notificados ao Sistema de Informação de Agravos de Notificação (SINAN), de 2006 a 2013. Os resultados mostraram aumento nas taxas de incidência de coqueluche no Brasil, a partir de 2011. Em 2013, foram confirmados 6.523 casos de coqueluche no país, três vezes o número de casos confirmados em 2011, com incidência geral de 3,24 /100.000 habitantes e incidência em menores de um ano de 125,82/100.000 habitantes, as maiores durante o período estudado. As crianças menores de um ano foram as mais acometidas pela doença em todas as macrorregiões. Em 2013, todas as regiões, exceto a região sul, apresentaram suas maiores taxas de incidência geral, com destaque para as regiões sudeste e centro-oeste com 4,0 e 3,1 por 100.000 habitantes, respectivamente. As maiores taxas de letalidade foram observadas na faixa etária menor de dois meses de idade, variando de 4,0% (2008) a 9,5% (2010). As taxas de letalidade foram maiores em crianças menores de seis meses em todas as regiões, sendo as regiões nordeste e sudeste as que apresentaram maiores taxas ao longo dos anos, exceto em 2013, quando o centro-oeste superou o nordeste. Houve predomínio dos casos nos meses mais quentes, entre novembro e março. A maioria das hospitalizações ocorreu na faixa etária de menores de um ano, principalmente em menores de quatro meses, cuja frequência de hospitalização ficou em torno de 75%. A tosse e o paroxismo foram os sintomas mais frequentes, independente da faixa etária, e a cianose foi importante sintoma nos menores de dois meses, com uma frequência de 80% nos casos confirmados desta faixa etária. A complicação mais comum foi pneumonia (13,93%), principalmente na faixa etária menor de dois meses, com frequência de 27,5%. O critério mais utilizado para diagnóstico de coqueluche foi o clínico, seguido pelo laboratorial que aumentou a partir de 2011, ano em que foi responsável por 49,9% dos diagnósticos. A maioria dos casos confirmados (51%) não relatou contato prévio com casos suspeitos ou confirmados de coqueluche, no entanto quando presente, a maioria dos contatos ocorreu no domicílio (70,6%). Os resultados mostraram aumento dos casos de coqueluche no Brasil, a partir de 2011, com as maiores taxas de incidência, hospitalizações, complicações e letalidade na faixa etária de menores de um ano / Pertussis has reemerged as important public health problem in many countries, despite the high childhood vaccination coverage. The general aim of this study was to evaluate the morbimortality of pertussis in Brazil, and the specific objectives were: estimate the annual mortality, incidence and case-fatality rates, general and by age group, by federative units and country\'s regions; evaluate the disease seasonality; estimate the annual hospitalization rates by age group and verify the clinical characteristics, contact history and the previous vaccination status of the reported pertussis cases. Methods: Descriptive study, based on the pertussis cases reported to the Notifiable Diseases Information System (SINAN), from 2006 to 2013. In 2013, there were 6.523 confirmed pertussis cases in the country, three times the number of confirmed cases in 2011, with general incidence of 3.24/100,000 inhabitants, and incidence in children under one year of age of 125.82/100,000 inhabitants, the highest during the study period. Pertussis incidence rates were higher in children under one year old in all macroregions during the study. In 2013, higher general incidence rates were observed in all regions, except the south, particularly the southwest and Midwest with 4.0 and 3.1 per 100,000 inhabitants, respectively. The highest case-fatality rates were observed in infants under two months of age, varying from 4.0% (2008) to 9.5% (2010). Case-fatality rates were higher in children under six months in all regions; the northeast and southeast had the highest rates throughout the studied years, except in 2013, when the Midwest surpassed the northeast. More cases were reported in the warmer months, between November and March. Most hospitalizations occurred in the age group of children under one year old, mainly those under four months, for whom hospitalization rates were close to 75%. Cough and paroxysm were the most frequently symptoms, regardless of age, and cyanosis was important in children under two months, occurring in 80% of confirmed cases in this age group. The most common complication was pneumonia (13.93%), mainly in children under two months of age (27.5%). Clinical criteria were most frequent used for diagnosis, followed by laboratory, which increased since 2011, when 49.9% of cases had laboratory-confirmed diagnosis. Most confirmed cases (51%) had no recognized previous contact with pertussis cases. Among those with recognized previous contact, it mostly occurred at residence (70.6%).The results showed an increase in pertussis cases in Brazil, since 2011, with the highest incidence and lethality rates in children under one year of age

Orientadores: Mônica Corso Pereira, Ilma Aparecida Paschoal, Ivete Alonso Bredda Saad / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T19:56:31Z (GMT). No. of bitstreams: 1 Ferraresso_Amanda_M.pdf: 1661408 bytes, checksum: 4e7bfa4f33f4937d9eb361e7a9a60e42 (MD5) Previous issue date: 2013 / Resumo: A Esclerose Lateral Amiotrófica (ELA) é uma desordem progressiva que envolve a degeneração dos neurônios motores em todos os níveis. A falência respiratória é a principal causa de morte nos pacientes com ELA e está diretamente relacionada com a disfunção muscular respiratória, em geral será tardia e precipitada por uma infecção respiratória. Objetivos: (1) Avaliar clínica e funcionalmente o comprometimento respiratório dos indivíduos portadores de esclerose lateral amiotrófica (ELA) e sua evolução com um programa de exercícios respiratórios e orientações domiciliares. (2) Traduzir para a língua portuguesa e avaliar a reprodutibilidade mediata da aplicação do questionário Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), em pacientes com ELA nascidos no Brasil. (3) Buscar a detecção precoce de distúrbios da deglutição por meio de questionários específicos e do exame salivograma. (4) A partir da análise dos desfechos clínicos (pacientes sem suporte pressórico, ventilação invasiva (VI) ou óbito), avaliar se alguma das medidas como capacidade vital forçada (CVF), pressões respiratórias máximas (PImax= pressão inspiratória máxima e PEmax= pressão máxima expiratória), pico de fluxo de tosse (PFT), questionários doença-específicos: amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) e amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-40), ajudariam na previsão do prognóstico da doença. Metodologia: foi realizado um estudo de coorte prospectivo, não controlado. No período de maio de 2010 a dezembro de 2011, todos os pacientes com diagnóstico de ELA, que frequentavam o ambulatório de doenças neuromusculares foram considerados para participar do estudo. O questionário ALSFRS-R foi aplicado no início da pesquisa e após 15 dias, para o processo de tradução e avaliação do instrumento. Foram avaliadas trimestralmente as variáveis de CVF (sentado ? supino), PImax, PEmax, PFT, SpO2 e questionários doença-específicos (ALSFRS-R e ALSAQ-40), ao longo de um período de 18 meses, exceto o radiograma de tórax e salivograma, avaliados somente ao início da pesquisa. Na evolução dos pacientes que participaram do programa de exercícios respiratórios, os pacientes foram separados em dois grupos (F1 e F2), com maior e menor número de sessões de fisioterapia, respectivamente. Resultados: Foram considerados para inclusão na pesquisa 32 pacientes, sendo incluídos 14 indivíduos efetivamente. A um nível de 5% foi encontrada significativa correlação entre as notas obtidas no questionário ALSFRS-R (p=0,001) nos dois momentos, o que permitiu a validação da versão na língua portuguesa. Das variáveis comparadas entre os grupos F1 e F2 apenas o PFT foi diferente entre os grupos, com valores de 125 e 225 L/min respectivamente (p=0,03). O PFT também foi a única variável que mostrou diferença entre o grupo de VI ou óbito vs pacientes sem suporte pressórico, com valores de 140 e 225 L/min, respectivamente (p= 0,007). Conclusões: O PFT, um exame simples, de fácil manuseio entre os clínicos e de baixo custo, pode ter um papel na avaliação do prognóstico destes doentes, além de auxiliar a traçar condutas que poderiam beneficiá-los em uma fase de maior comprometimento funcional / Abstract: The Amyotrophic Lateral Sclerosis (ALS) is a progressive disorder involving degeneration of motor neurons at all levels. Respiratory failure is the leading cause of death in patients with ALS and is directly related to respiratory muscle dysfunction, usually late and will be precipitated by a respiratory infection. Objectives : ( 1 ) To evaluate the clinical and functional respiratory impairment of individuals with amyotrophic lateral sclerosis (ALS ) and its evolution with a program of breathing exercises and guidance at home; ( 2 ) Translate to Portuguese and to assess the mediated reproducibility of the Amyotrophic Lateral Sclerosis Functional Rating Scale -Revised ( ALSFRS -R ) questionnaire, in patients with ALS born in Brazil; ( 3 ) Search for the early detection of swallowing disorders through specific interviews and salivagram examination; ( 4 ) iii) From the analysis of clinical outcomes data to assess whether lung function and disease specific questionnaires may help predict the prognosis of patients with ALS. Methods: we conducted a prospective cohort study, not controlled. From May 2010 to December 2011, all patients diagnosed with ALS, who attended the outpatient neuromuscular diseases were considered for the study. The ALSFRS -R questionnaire was administered at baseline and after 15 days for the translation process and evaluation of the instrument. Were evaluated quarterly variables FVC ( sitting / supine) , MIP, MEP , PCF , SpO2 and disease-specific questionnaires ( ALSFRS - R and ALSAQ - 40 ) over a 18 month period , except the chest X-ray and salivagram, evaluated only the beginning of research. The outcome of patients who participated in the program of breathing exercises, patients were separated into two groups (F1 and F2), with the highest and lowest number of physiotherapy sessions, respectively. Results: We considered for inclusion in the study 32 patients, including 14 individuals effectively. At a level of 5 % was found significant correlation between the scores obtained in the ALSFRS -R questionnaire (p = 0.001) in the two periods, which allowed the validation of the Portuguese version. Variables compared between groups F1 and F2 only the PFT was different between groups , with values of 125 and 225 L / min, respectively ( p = .03 ) . The PFT was also the only variable that showed a difference between the VI group of patients without or death vs. pressure support , with values of 140 and 225 L / min, respectively (p = 0.007). Conclusions : The PFT , a simple test , easy handling between the clinical and cost , may have a role in assessing the prognosis of these patients , and help to trace behaviors that could benefit them in a stage of greater functional impairment / Mestrado / Clinica Medica / Mestra em Ciências

Les enfants nés prématurément, et plus particulièrement les grands prématurés nés avant<p>31 semaines d’âge gestationnel, sont à haut risque de contracter des infections. La<p>vaccination peut prévenir certaines infections, dont la coqueluche qui est causée par la<p>bactérie Bordetella pertussis (Bp). Cependant, cette maladie infectieuse hautement<p>contagieuse est en recrudescence depuis plusieurs années malgré une bonne couverture<p>vaccinale. La morbidité et surtout la mortalité de la coqueluche affectent plus<p>particulièrement les jeunes enfants, incomplètement ou non encore vaccinés.<p>Il existe deux types de vaccins contre B. pertussis :les vaccins de première génération à<p>cellules entières et les vaccins acellulaires, plus récents. Suite à l’apparition d’effets<p>secondaires causés par le vaccin à cellules entières, les vaccins acellulaires, comprenant<p>seulement un certain nombre d’antigènes purifiés de B. pertussis, sont utilisés en Belgique<p>comme dans de nombreux autres pays industrialisés.<p>L’immunité protectrice contre B. pertussis fait appel tant à l’immunité cellulaire qu‘à<p>l’immunité humorale. De nombreuses études ont démontré une production d’anticorps<p>spécifiques aux antigènes de B. pertussis suite à l’administration des différents types de<p>vaccins. Par contre, peu d’entre elles ont analysé la réponse d’immunité cellulaire spécifique<p>caractérisée, entre autres, par une sécrétion d’Interféron-gamma (IFN-& / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Malgré l’existence de différents vaccins protecteurs à l’égard des infections par B. pertussis, la coqueluche reste une maladie infectieuse fréquente et est encore actuellement responsable de 300.000 décès par an dans le monde. Une meilleure compréhension des réponses immunitaires induites par les principaux facteurs de virulence de B. pertussis est donc importante afin d’optimaliser la vaccination. Alors que le rôle des anticorps dans la protection contre la coqueluche est reconnu depuis de nombreuses années, celui des réponses d’immunité cellulaire a été identifié mais est moins bien caractérisé. <p>Dans ce travail, nous avons analysé différents aspects des réponses d’immunité cellulaire induites par deux antigènes majeurs de B. pertussis, l’hémagglutinine filamenteuse (FHA) et la toxine pertussique (PT) chez des nourrissons. Nous avons étudié la persistance des réponses spécifiques des antigènes de B. pertussis après la primo vaccination des nourrissons et caractérisé différents facteurs qui modulent ces réponses, nous permettant ainsi de comprendre l’hétérogénéité des réponses d’immunité cellulaire observées tant qualitativement que quantitativement. <p>Nous avons montré que les réponses immunitaires spécifiques de la FHA et de la PT pouvaient persister jusqu’à neuf mois après la dernière administration du vaccin contre la coqueluche. Ces réponses immunitaires sont caractérisées par une production d’interféron-gamma (IFN-&61543;) par les cellules sanguines circulantes (PBMC), par une prolifération lymphocytaire ainsi que par une production d’anticorps. Bien que les lymphocytes T CD8+ participent à la sécrétion spécifique d’IFN-&61543; leur participation semble quantitativement moins importante que celle des lymphocytes T CD4+ et dépendante de ces derniers. Cependant, les PBMC de certains enfants vaccinés ne produisent pas ou peu d’IFN-&61472;&61543; après stimulation in vitro par les antigènes de B. pertussis. Cette inhibition, voire absence, de réponse immunitaire de type Th1 spécifique est associée à une sécrétion constitutive d’IL-10 par les monocytes ou à la présence de lymphocytes T CD8+. Enfin, étant donné que la FHA est inductrice d’IL-10 dans un modèle in vitro murin, nous avons analysé son effet sur la production in vitro de cette cytokine par les cellules dendritiques humaines (DCs). Nous avons montré que la FHA induit bien une production d’IL-10 par les DCs mais également les productions d’IL-12p70, d’IL-6 et d’IL-23, cytokines impliquées dans la différenciation des lymphocytes T naïfs en lymphocytes T effecteurs Th1 ou Th17. Parallèlement, nous avons testé une forme tronquée de FHA, la FHA 44 qui est également protectrice dans un modèle murin d’infection par B. pertussis. Nous avons montré que cette FHA tronquée n’induit pas de production d’IL-10 tout en induisant une production d’IL-12p70 et d’IL-23 par les DCs. La forme moléculaire de FHA présente dans les vaccins joue donc un rôle déterminant sur le type de réponses immunitaires induites et le remplacement de la FHA native dans les vaccins acellulaires par la FHA 44 devrait potentiellement permettre une meilleure réponse IFN-& / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Voluntary coughs are used as a diagnostic tool to detect lung diseases. Understanding the mechanics of a cough is therefore crucial to accurately interpreting the test results. A cough is characterised by a dynamic compression of the airways, resulting in large flow velocities and producing transient peak expiratory flows. Existing models for pulmonary flow have one or more of the following limitations: 1) they assume quasi-steady flows, 2) they assume low speed flows, 3) they assume a symmetrical branching airway system. The main objective of this thesis is to develop a model for a cough in the branching pulmonary airway system. First, the time-dependent one-dimensional equations for flow in a compliant tube is used to simulate a cough in a single airway. Using anatomical and physiological data, the tube law coupling the fluid and airway mechanics is constructed to accurately mimic the airway behaviour in its inflated and collapsed states. Next, a novel model for air flow in an airway bifurcation is constructed. The model is the first to capture successfully subcritical and supercritical flows across the bifurcation and allows for free time evolution from one case to another. The model is investigated by simulating a cough in both symmetric and asymmetric airway bifurcations. Finally, a cough model for the complete branching airway system is developed. The model takes into account the key factors involved in a cough; namely, the compliance of the lungs and the airways, the coughing effort and the sudden opening of the glottis. The reliability of the model is assessed by comparing the model predictions with previous experimental results. The model captures the main characteristics of forced expiatory flows; namely, the flow limitation phenomenon (the flow out of the lungs becomes independent of the applied expiratory effort) and the negative effort dependence phenomenon (the flow out of the lungs decreases with increasing expiratory effort). The model also gives a good qualitative agreement with the measured values of airway resistance. The location of the collapsed airway segment during forced expiration is, however, inconsistent with previous experimental results. The effect of changing the model parameters on the model predictions is therefore discussed.