A disfunção das pregas vocais (DPV) é caracterizada por movimento paradoxal de fechamento das pregas vocais, ocorrendo de forma episódica e involuntária durante a inspiração, levando à obstrução das vias aéreas. Os pacientes que apresentam DPV costumam não responder ao tratamento indicado para asma, levando ao uso inapropriado de corticóides sistêmicos com efeitos colaterais, freqüentes passagens em setores de emergência, hospitalizações por vezes desnecessárias e, com menos freqüência, intubação e traqueostomia. O objetivo principal deste estudo foi o de investigar a relação desta problemática com a economia psíquica destes pacientes, no que diz respeito à psicogênese e as possibilidades de tratamento por meio do método clínico de investigação e tratamento psicanalíticos. Para isto, foram incluídos 5 pacientes do sexo feminino, com idades entre 30 e 55 anos, que foram acompanhadas em tratamento psicanalítico no ambulatório do Serviço de Imunologia Clínica e Alergia do Instituto Central do HCFMUSP. Constatamos que a DPV aparece de maneira singular na vida de cada paciente investigada, porém com características peculiares que indicam uma localização psíquica capaz de operar como uma satisfação inconsciente frente a um conflito anterior. A princípio, abordar a paciente como se esta não possuísse asma pode levar a uma reação negativa, interpretada por elas como um fingimento ou uma estratégia consciente de obter ganhos primários. A interlocução entre o psicanalista e os demais profissionais da equipe mostra-se de significativa importância / Vocal fold dysfunction (VFD) is characterized by paradoxical movement of closing of the vocal folds, occurring of irregularly and involuntary form during the inspiration, leading to the blockage of the aerial ways. The patients who present VFD do not answer to the treatment indicated for asthma, leading to the unnecessary use of systemic steroids with collateral effect, frequent visits in emergency sectors, hospitalizations and, sometimes, intubations and tracheotomies. The main objective of this study was to investigate the relation of this problematic and the psychic economy of these patients, in whom it says respect to psychogenic explanation and the possibilities of psychoanalytical treatment. For this, 5 patients of the feminine sex had been enclosed, with ages between 30 and 55 years, that had been followed in psychoanalytical treatment in the clinic of the Service of Clinical Imunologia and Allergy of the Central Institute of the HCFMUSP. We evidence that the VFD appears in singular way in the life of each investigated patient, however with peculiar characteristics that indicate a psychic localization capable to operate as an unconscious satisfaction to a previous conflict. To approach the patient as if this did not possess asthma can lead to a negative reaction, interpreted for them as a deceit or a conscientious strategy to get primary profits. The interlocution between the psychoanalyst and the members of the team reveals of significant importance

Este estudo tem como objetivo, descrever a microbiota intestinal de pacientes com retocolite ulcerativa grave, em tratamento clínico, antes e após retocolectomia com anastomose de bolsa ileal ao canal anal. Comparou-se a flora bacteriana do íleo terminal e do reto no pré-operatório com a flora encontrada na bolsa ileal após dois e oito meses do fechamento da ileostomia e com a flora do íleo terminal e do reto de um grupo controle. Observou-se que a Veillonella sp foi a bactéria mais freqüentemente encontrada em todos os grupos. Não houve diferenças significativas entre a flora intestinal do grupo controle e dos pacientes com retocolite ulcerativa / The aim of this study is to describe the intestinal microbiota of patients with severe ulcerative colitis, under clinical treatment, before and after proctocolectomy and ileal pouch-anal anastomosis. Intestinal flora of distal ileum and rectum before surgery was compared with the flora found in ileal pouch after two and eight months after ileostomy closure and with the flora of distal ileum and rectum of controls. Veillonella sp was the most frequent microorganism found in all groups. There were no significant differences between the intestinal microbiota found in controls and in patients with ulcerative colitis

INTRODUÇÃO: Raramente os estudos populacionais sobre disfunção erétil (DE) incluem homens com menos de 40 anos de idade e, quando o fazem, não há detalhamento dos vários fatores e conseqüências potencialmente associados a esta condição. O objetivo deste estudo foi avaliar a prevalência da disfunção erétil e seus fatores associados em amostra da população brasileira de 18 a 40 anos. MÉTODOS: O Estudo da Vida Sexual do Brasileiro (EVSB) entrevistou 7.022 homens e mulheres em locais públicos de 18 grandes centros urbanos do Brasil por meio de um questionário auto-responsivo que abordava aspectos demográficos, de saúde, de hábitos e dificuldades sexuais, sendo a presença de disfunção erétil avaliada por questão única. De todo o grupo, 1.947 eram do sexo masculino e da faixa etária de 18 a 40 anos. RESULTADOS: Um total de 35% dos indivíduos do estudo tinha queixas de disfunção erétil (73,7% dos quais sendo DE mínima e 26,3% moderada/completa). O relato de DE foi mais freqüente na faixa etária mais jovem (18 a 25 anos), nos indivíduos da raça negra, parda ou amarela e no grupo que tinha menor escolaridade; na analise de regressão múltipla, porém, dentre esses fatores, somente o baixo grau de instrução permaneceu fortemente associado à presença de DE. Estado civil e situação empregatícia não influenciaram a prevalência de problemas de ereção. Não foi encontrada associação de maior freqüência de DE em homens com histórico de tabagismo, obesidade, diabetes, hipertensão, sedentarismo, cardiopatia, hiperlipidemia, depressão ou ansiedade. Orientação sexual não se relacionou com maior prevalência de DE, porém a falta de informações sobre sexo durante a vida, dificuldades no início da vida sexual e a ausência do hábito de masturbação correlacionaram-se com uma maior chance de queixas de DE. Para toda a população do estudo, as fontes recentes de informação sobre sexo foram principalmente os livros e revistas, seguidos pela conversa com a parceira e com amigos, sendo a orientação médica xvi menos citada pelo grupo. Outros problemas sexuais, como ejaculação precoce, retardada e diminuição de libido, foram mais freqüentes em homens com DE, em comparação aos homens sem esta disfunção. Menos de 10% dos homens com DE relataram já terem recebido tratamento para o problema e cerca de 3% de indivíduos sem queixas de DE declararam terem feito uso de medicações para melhora da ereção. A DE causou impacto negativo em várias áreas da vida dos portadores desta disfunção: no relacionamento com a parceira e amigos, no trabalho e lazer, além da auto-estima dos indivíduos com o problema, causando também auto-avaliação negativa quanto ao desempenho e a vida sexual. CONCLUSÕES: A prevalência de DE, mesmo na população abaixo de 40 anos, foi alta, com preponderância da forma leve. Baixa escolaridade e problemas na iniciação sexual associaram-se com a presença de DE e, provavelmente devido a pouca idade dos indivíduos da amostra, não foi encontrada associação de DE com problemas de saúde de causa orgânica. Ações nas áreas de educação e prevenção teriam um impacto positivo no controle de disfunção erétil na população / INTRODUCTION: Populational studies in erectile dysfunction (ED) rarely included subjects less than 40 years old and, when this was done, there were no information on the several factors and consequences potentially associated with this condition. The objective of this study was to evaluate the prevalence of erectile dysfunction (ED) and associated factors in a sample of Brazilian men aged 18 to 40 years old. METHODS: The Brazilian Sexual Life Study interviewed 7,022 men and women in public places of 18 major Brazilian cities using a self-administered questionnaire that investigated social-demographic and health aspects, life habits and sexual difficulties, including ED, which was assessed by a single question. From the whole group, 1,947 were men between 18 and 40 years old. RESULTS: Complaints of ED were found in 35.0% of the study subjects (73.7% had mild ED; 26.3% moderate/complete ED). Greater frequency of ED report was seen in younger subjects (18 to 25 years), in men of black, mixed or Asian races, and in the group with less education; in the multiple regression analyses, among these factors, only low level of education remained strongly associated with ED diagnosis. Employment and marital status didnt affect the prevalence of erection problems. No association was seen between ED report and medical history of smoking, obesity, diabetes, hypertension, sedentary lifestyle, cardiopathy, hyperlipidemia, depression or anxiety. Sexual orientation was not correlated to greater ED frequency, but the lack of information about sex, difficulties in the beginning of sexual life and absence of masturbation habit were related to an increased chance of ED diagnosis. Recent sources of information about sex were mainly books and magazines, followed by talking to the partner and friends, being medical advice less mentioned by the whole study population. Other sexual disorders such as premature or retarded ejaculation, and decreased libido were more frequent in men with ED, in comparison to men without this dysfunction. Less than 10% of men with ED xix reported that ever received treatment for this problem, and about 3% of subjects without ED complaints admitted the use of medications to improve erectile function. ED caused negative impact in several aspects of life: in the relationship with partner and friends, in work and leisure, besides mens self-esteem, causing also a negative self-evaluation of sexual life and performance. CONCLUSIONS: Prevalence of ED in this population below 40 years of age was high, mostly of mild severity. Low education and problems in sexual initiation correlated to ED occurrence and, probably due to the sample subjects young age, no association was found with health problems of organic causes. Measures in the fields of education and prevention would have a positive impact in the control of erectile dysfunction in the population

Dor facial atípica (DFA) é uma condição álgica crônica destacada pela etiopatogenia ainda desconhecida e pela característica rebelde aos tratamentos vigentes. O objetivo deste estudo é avaliar o limiar e padrões de excitabilidade cortical de doentes com DFA através de Estimulação Magnética Transcraniana (EMT) e compará-los a controles saudáveis, além de avaliar a eficácia terapêutica da EMT repetitiva (EMTr) ativa em doentes com DFA comparados à EMTr placebo. Durante o período de março de 2010 a dezembro de 2013 foram avaliados 29 doentes com DFA - os quais preencheram os critérios segundo a classificação proposta pela Associação Internacional de Cefaleia (2004) - e 28 controles saudáveis. A avaliação foi iniciada com a investigação da excitabilidade cortical bilateral. Em seguida, os doentes foram aleatorizados em dois grupos (ativo e placebo) para o tratamento com EMTr sobre o córtex motor primário na área de representação da face, esquematizado da seguinte forma: cinco sessões consecutivas para a fase de indução, e uma sessão semanal (pelo período de oito semanas) para a de manutenção; frequência excitatória de 10Hz; 80% do limiar motor de repouso; e 3000 pulsos no total por sessão. Os doentes foram avaliados quanto às características dolorosas no momento basal, no dia sete após a semana de indução, e nos dias 21, 30 e 60 para acompanhamento na fase de manutenção. Em todas as avaliações, utilizou-se os seguintes questionários validados para a língua portuguesa: Inventário Breve de Dor; DN4, Inventário de Sintomas de Dor Neuropática, Questionário de descritores breve de dor McGill e Questionário de qualidade de vida SF-36. Os doentes do grupo ativo e placebo apresentaram excitabilidade cortical inicial diferenciada em relação aos controles nos padrões de inibição e facilitação intracortical (p < 0,001). Ao final da última avaliação, os doentes do grupo ativo apresentavam padrões de excitabilidade cortical mais próximos dos controles do que os doentes do grupo placebo, embora sem significância estatística. Não houve diferença entre os grupos ativo e placebo em todas as avaliações quanto às características de dor e de qualidade de vida, sendo que ambos apresentaram melhora da dor. Conclui-se que há diferenças neurofisiológicas entre os doentes com DFA e os controles, e que isso pode ser modificado através do EMTr. A ausência de efeito terapêutico da EMTr neste estudo indica que mais estudos utilizando-se outros parâmetros para a verificação da eficácia da EMTr na DFA são necessários / Atypical facial pain (AFP) is a chronic condition with unknown physiopathology and refractory characteristics to the gold standard treatment. The aim this study was to compare the patterns of cortical excitability between AFP and health subjects (HS), and to assess the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in AFP patients. Twenty-eight HS and 29 patients with AFP were included according to the IHS criteria (2004). Participants underwent a cortical excitability battery bilaterally in the primary motor cortex (M1) representation of the masseter muscle. They were then randomized into active and sham rTMS groups. rTMS was performed over the contralateral motor cortex in the representation area of the face daily for a week and weekly for eight weeks in a total of 13 sessions (5 induction and 8 maintenance sessions). All participants received 10 Hz rTMS, at 80% of the rest motor threshold (total of 3000 pulses per session). Sham rTMS was performed with an identical sham coil that emitted a similar sound to the active one. Patients were clinically assessed at baseline, after the induction phase (one week) and after 21, 30 and 60 days after the beginning of the study. Evaluations included the following validated questionnaires to the Brazilian Portuguese language: brief pain inventory; DN-4; Neuropathic pain symptoms inventory, McGill pain questionnaire brief version and quality of life questionnaire SF-36. At the baseline assessment, patients with AFP showed defective intracortical excitability inhibition and facilitation (p < 0.001) compared to HS. After the final evaluation, the patients from the active group had cortical excitability patterns closer to HS than the patients from the sham group, although there was no significant difference. There was no difference between patients that underwent active and sham rTMS about their pain characteristics and quality of life; both had pain improvement. In conclusion, there are neurophysiological differences between patients with AFP and HS, which could be modified with rTMS. The absence of a therapeutic effect of rTMS on pain in this study indicates the need of more research with other TMS parameters to check the efficacy of rTMS in AFP

A doença diverticular dos cólons (DDC) é relacionada à civilização, industrialização e à dieta. Estudos fisiológicos demonstraram que uma pressão intraluminal elevada, bem como alterações estruturais adquiridas da parede intestinal parecem ser fator decisivo, que se intensificam com o envelhecimento. Estas alterações podem ser causadas por alterações no tecido muscular e tecido conjuntivo relacionados ao metabolismo do colágeno e elastina, que presumivelmente pode ser geneticamente determinada. Sabe-se que pacientes com desordens genéticas do gene da elastina (ELN), como a estenose aórtica supravalvar e a cutis laxa, podem manifestar hérnia, diverticulose e disfunção urinária. Recentemente, foi demonstrado mutação pontual no exon 20 do ELN em pacientes com hérnia inguinal. No presente estudo investigamos o polimorfismo do exon 20 do ELN em 14 pacientes com DDC e 26 controles. A presença de mutação foi verificada por eletroforese conformacional de fita simples e sequenciamento automático. Demonstramos bandas anormais em alguns pacientes, que representaram uma mutação não conservativa: substituição de um nucleotídeo (AGT->GGT) no códon 422 do gene da ELN em cinco pacientes com DDC. Nenhum indivíduo controle estudado apresentou este tipo de mutação. Observamos uma associação significante (P=0,003) desta mutação com o desenvolvimento da DDC e risco relativo 3,89 vezes maior (intervalo de confiança de 95%: 2,21-6,83) dos indivíduos com esta mutação desenvolver DDC. Esta mutação troca Serina, um aminoácido não polar, por glicina, um aminoácido neutro, alterando a estrutura hidrofóbica da elastina e secundariamente a estrutura da fibra elástica. Esta alteração pode promover perda da complacência da parede intestinal e o desenvolvimento de divertículo / Colonic diverticular disease (CDD) is related to civilization, industrialization and diet. Physiological studies demonstrated that increased intraluminal pressures as well as acquired structural changes of the intestinal wall seem to be decisive factors, which intensify during ageing. These changes may be due to alterations of the musculare and connective tissues and are related to collagen and elastin metabolism, which presumably can be genetically determined. It is known that patients with genetic disorders of elastin gene (ELN), such as supravalvular aortic stenosis and cutis laxa, may also manifest hernias, diverticulosis and bladder dysfunction. Recently, punctual mutations were demonstrated in ELN exon 20 of inguinal hernia patients. In the the present study, the polymorphism ELN exon 20 was tested in 14 patients with CDD and in 26 controls. Mutations were sought by singlestrand conformation polymorphism and by automatical sequence. An abnormal band was demonstrated in some patients, representing a missense mutation: a single nucleotide substitution (AGT->GGT) was detected in codon 422 in five patients with CDD. There is a substituion of serine, a nonpolar amino acid, by glycine, na uncharged one. No controls showed this punctual mutation(P=0,003), and the odds ratio for development of CDD was 3.33 (95% confidence interval:1,98-5,62). As a consequence of this substitution, the hydrophobic structure of elastin and of elastic fiber may promote a loss of compliance of the intestinal wall and development of diverticula

L’hypothyroïdie congénitale (HC) est une maladie relativement fréquente, touchant un nouveau-né sur 3000-4000, et dont la majorité des cas sont causés par un défaut dans le développement embryonnaire de la glande. Il existe plusieurs arguments en faveur d’une cause génétique dans une minorité de ces dysgénésies thyroïdiennes mais, à ce jour, seuls quelques cas ont put être reliés à une mutation dans l’un ou l’autre de trois gènes codant pour des facteurs de transcription impliqués dans le développement de la thyroïde (TITF1, PAX8 et FOXE1).<p>Au cours de notre travail de thèse, nous avons caractérisé la 6ème mutation du gène PAX8 à l’état hétérozygote, dans un cas familial d’HC. Nous avons étudié l’impact fonctionnel de cette altération qui entraîne une perte de liaison de la protéine mutée à une séquence cible spécifique, ainsi qu’une diminution drastique de la synergie de transactivation en association avec Titf1. Le phénotype des patients est également intéressant à plus d’un titre. En effet, nous avons pu observer que les mutations de PAX8 sont compatibles avec le développement d’une thyroïde en place et de taille normale à la naissance, pouvant conduire à un diagnostic erroné de dyshormonogenèse. De plus, un des trois patients présente un phénotype rénal qu’il est tentant de relier à la mutation de PAX8 étant donné que ce gène est exprimé durant le développement de cet organe, tout comme dans la thyroïde.<p>Notre travail a également consisté en l’élaboration d’une librairie SAGE du bourgeon thyroïdien en développement, afin de rechercher de nouveaux gènes candidats impliqués dans le développement de la glande thyroïde. Grâce à une technique d’amplification d’ARN, nous avons obtenu une librairie d’environ 94.000 étiquettes à partir de bourgeons thyroïdiens provenant d’embryons de souris au 11ème jour de développement. Cette librairie nous a permis d’identifier une nouvelle isoforme du transcrit de Titf1 modifiant l’extrémité 3’-non codante du messager, ainsi qu’un gène de fonction inconnue mais dont le profil d’expression ainsi que sa grande conservation au cours de l’évolution laissent suggérer un rôle important, tant dans les tissus embryonnaires que dans les tissus adultes.<p>Ces deux découvertes valident le caractère prédictif de notre librairie qui constitue un outil de choix pour l’identification de nouveaux gènes de développement thyroïdien et donc de nouveaux candidats pour l’étude des mécanismes étiopathogéniques à la base des dysgénésies thyroïdiennes.<p>/<p>Congenital hypothyroidism (CH) is a relatively frequent disease affecting 1 every 3000-4000 newborns. The majority of CH cases are caused by a defect in the embryonic development of the gland. There exists several arguments in favor of a genetic cause for a minority of these thyroid dysgeneses but, to this day, only a few cases have been related to a mutation in one of three genes coding for transcription factors implicated in thyroid development (TITF1, PAX8 and FOXE1).<p>In the course of this work, we have caracterized the 6th mutation of the PAX8 gene, in the heterozygous state, in a familial case of CH. We have studied the functional impact of this modification which leads to a loss of the protein’s DNA-binding properties and to a severe reduction in the transactivation synergy in association with Titf1. The phenotype of the patients presents also interesting features. Indeed we have observed that the PAX8 mutations are compatible with the development of an in-place, normal-sized thyroid at birth, which could lead to an erroneous diagnostic of dyshormonogenesis. Moreover, one of the three patients presents with a renal phenotype (unilateral kidney agenesis) which is tempting to relate to the PAX8 mutation, given this gene is expressed during kidney development.<p>Our work also consisted in the generation of an embryonic thyroid bud SAGE library, which we used to search for new candidate genes implicated in thyroid development. With the help of a RNA amplification technique, we obtained a library of roughly 94.000 tags starting from mous thyroid buds at E11. This library allowed us to identify a new Titf1 splicing variant modifying the 3’-UTR of the transcript, and a gene of unknown function. The latter’s expression profile and high conservation throughout evolution suggest a crucial role in embryonic as well as adult tissues.<p>These two findings validate the predictive character of our library which constitutes a powerful tool to identify new thyroid developmental genes and new candidate genes for the study of the etiopathogenic mecanisms responsible for CH.<p><p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Les pneumonies sont la première cause de mortalité par maladie infectieuse dans le monde chez les enfants. Les objectifs étaient d'identifier les causes microbiologiques des pneumonies communautaires chez les enfants de moins de 5 ans dans les pays émergents et en développement et les déterminants associés à leur sévérité en termes d'hypoxémie à l'admission et de mortalité. Une étude cas-témoins multicentrique hospitalière a été menée par le réseau GABRIEL dans 9 sites des pays suivants : Cambodge, Chine, Haïti, Inde (2 sites), Madagascar, Mali, Mongolie et Paraguay. Les cas étaient des enfants hospitalisés, âgés de 2 à 60 mois et atteints de pneumonie radiologiquement confirmée ; un témoin par cas du même centre, sans signe évocateur de pneumonie était recherché. Un appariement fréquentiste sur la période et la classe d'âge était effectué. Des prélèvements respiratoires ont été réalisés chez tous les sujets pour identifier 19 virus, 5 bactéries et les sérotypes de Streptococcus pneumoniae par biologie moléculaire. Pour les cas, des prélèvements supplémentaires de sang et de liquide pleural étaient effectués. Les étiologies des pneumonies ont été estimées par le calcul de la fraction attribuable populationnelle après régression logistique multivariée. Les facteurs associés à l'hypoxémie à l'admission - déterminés chez les patients atteints de pneumonie - ont été identifiés par régression logistique multivariée ; les facteurs associés à la mortalité hospitalière à 14 jours ont été quantifiés par modèle de Cox bivarié. Parmi les 888 cas et 870 témoins analysés, les agents causaux des pneumonies après analyse multivariée étaient par ordre décroissant de fréquence : S. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus (hMPV), parainfluenza virus 1, 3 et 4, influenzavirus A et B et Mycoplasma pneumoniae. La fraction attribuable ajustée était de 42,2% (intervalle de confiance [IC] à 95% : 35,5-48,2%) pour S. pneumoniae, de 18,2% (IC à 95% : 17,4-19,0%) pour RSV et de 11,2% (IC à 95% : 7,5-14,7%) pour rhinovirus. Une importante hétérogénéité des étiologies entre pays a été identifiée. Parmi les 405 cas de pneumonie analysés pour l'étude de la gravité, 17,3% étaient hypoxémiques. La détection d'hMPV ou de RSV au niveau respiratoire était indépendamment associée à un risque accru d'hypoxémie (odds ratio ajusté [ORa]=2,4 ; IC à 95% : 1,0-5,8 et ORa=2,5 ; IC à 95% : 1,1-5,3, respectivement). La détection de S. pneumoniae dans le sang (hazard ratio brut [HRb]=4,6 ; IC95% : 1,5-14,0), un dosage de procalcitonine ≥50 ng/ml (HRb=22,4 ; IC à 95% : 7,3-68,5) et l'hypoxémie à l'admission (HRb=4,8, IC à 95% : 1.6-14.4) étaient prédictifs de surmortalité hospitalière ; ces associations subsistaient après ajustement sur l'âge, la période, le centre, la séropositivité HIV ou le statut nutritionnel. La majorité des pneumonies chez les enfants de moins de 5 ans dans les pays en développement peut être attribuée à S. pneumoniae, RSV, rhinovirus et hMPV. Les pneumonies hypoxémiantes chez les enfants sont liées à hMPV et RSV alors que les pneumonies liées à S. pneumoniae sont associées à un risque accru de décès. Ces résultats permettent d'identifier des priorités de prévention vaccinales et non-vaccinales / Pneumonia is the leading cause of death from infectious diseases in children worldwide. The objectives were to identify the etiologies of community-acquired pneumonia in children under 5 years in emerging and developing countries and the determinants associated with severity in terms of hypoxemia at admission and mortality. A hospital-based multicenter casecontrol study was conducted at 9 sites in the following countries: Cambodia, China, Haiti, India (2 sites), Madagascar, Mali, Mongolia and Paraguay. Cases were hospitalized children aged between 2 and 60 months, with radiologically confirmed pneumonia; a control was a patient from the same center, without any sign suggesting pneumonia. A frequentist matching by period and age category was made. Respiratory samples were taken from all subjects to identify 19 viruses, 5 bacteria and Streptococcus pneumoniae serotypes by molecular biology. For cases only, additional blood samples and pleural fluid were performed. The etiologies of pneumonia were estimated by calculating the population-attributable fraction after multivariate logistic regression. The factors associated with hypoxemia at admission were identified in patients with pneumonia by multivariate logistic regression; factors associated with 14-day in-hospital mortality were quantified by bivariate Cox model. Among the 888 cases and 870 controls analyzed, the causative agents of pneumonia after multivariate analysis migth be: Streptococcus pneumoniae, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus (hMPV), parainfluenza virus 1, 3 and 4, influenzavirus A and B, and Mycoplasma pneumoniae. The adjusted attributable fraction was 42.2% (95% confidence interval [CI]: 35.5-48.2%) for S. pneumoniae, 18.2% (95% CI: 17.4-19.0%) for RSV and 11.2% (95% CI: 7.5-14.7%) for rhinovirus. A significant heterogeneity in etiologies between countries was identified. Among the 405 pneumonia cases analyzed for the study of gravity, 17.3% were hypoxemic. Detection of hMPV or RSV from respiratory samples were independently associated with an increased risk of hypoxemia (adjusted odds ratio [aOR]=2.4, 95% CI: 1.0-5.8; aOR=2.5, 95% CI: 1.1-5.3, respectively). Detection of S. pneumoniae from blood (crude hazard ratio [cHR]=4.6, 95% CI: 1.5- 14.0), procalcitonin ≥50 ng/ml (cHR=22.4, 95 %: 7.3-68.5) and hypoxemia (cHR=4.8, 95% CI: 1.6- 14.4) were predictive of higher hospital mortality; these associations were consistent after adjusting for age, period, center, HIV or nutritional status. The majority of pneumonia in children under 5 years of age in developing countries might be attributable to S. pneumoniae, RSV, rhinovirus and hMPV. Hypoxemic pneumonia in children were related to RSV and hMPV infection while S. pneumoniae-related pneumonia was associated with an increased risk of death. These findings might guide future vaccinal or non vaccinal policies

Foram selecionados 231 indivíduos, no período de abril de 1997 a janeiro de 1998, divididos em dois grupos controle com 88 indivíduos e 143 pacientes com doença arterial coronária. Os pacientes foram subdivididos em dois grupos: 59 com angina estável e 84 com IAM. Foram analisadas as características clínicas, fatores de risco, pressão arterial sistólica e diastólica, perfil lipídico, glicemia, tabagismo, apoliproteína Al, apoliproteína B, lipoproteína (a), fibrinogênio, ácido úrico e hemograma completo. Análise multivariada mostrou que a idade, o HDL-colesterol, leucócitos e monócitos foram fatores de risco independentes para doença arterial coronária. / Between april 1997 and january 1998, 231 patients were selected and divided into two groups: control group with 88 patients and 143 patients with coronary artery disease. The latter group was then divided into two subgroups: 59 patients with stable angina and 84 patients with AMI. Clinical characteristics, risk factors, systolic and diastolic blood pressure, lipid profile, glycemia, smoking, apoliprotein Al, apoliprotein B, lipoprotein(a), fibrinogen, uric acid and total blood cell count were analyzed. Multivariate analysis showed age, HDL-cholesterol, leukocytes and monocytes as independent risk factors for coronay heart disease.

Endocardite infecciosa é uma doença associada à elevada morbidade e letalidade. O diagnóstico precoce e o reconhecimento de sua etiologia podem contribuir para o sucesso do tratamento antibiótico; entretanto, cerca de um quarto das endocardites permanece sem diagnóstico etiológico. Este estudo teve como objetivo principal identificar a frequência de endocardite por Bartonella spp. e Coxiella burnetii dentre as endocardites com culturas negativas comunitárias e avaliar os fatores preditores dessas infecções. Como objetivo secundário compararam-se as características clínicolaboratoriais e prognósticas entre as endocardites comunitárias com culturas negativas e positivas. Foram avaliados também os fatores associados à letalidade intra-hospitalar das endocardites com culturas negativas. Entre janeiro de 2004 e janeiro de 2009, foram investigados 369 episódios consecutivos de endocardite em pacientes atendidos no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Foram estudados os casos que ocorreram em adultos, classificados pelos critérios de Duke modificados como \"endocardite definida\" e de origem comunitária. Assim, foram incluídos 221 episódios de endocardite, 170 com culturas positivas e 51 com culturas negativas. Neste último grupo, foram feitas as pesquisas sorológicas (reação de imunofluorescência indireta) e histopatológica de Bartonella spp. e Coxiella burnetii. Consideraram-se positivos títulos de imunoglobulina G (IgG) >= 800 para Bartonella henselae e ou Bartonella quintana, e IgG antifase I para C. burnetii > 800. O estudo histopatológico das valvas cardíacas foi capaz de identificar morfologicamente a etiologia de 87% das endocardites com culturas negativas, enquanto que o método de Gram do tecido a fresco o fez em somente 10% dos casos. As endocardites com culturas negativas apresentaram maior frequência de dispneia à admissão (p=0,001), menor valor de proteína C reativa (p=0,009), menor Fração de Ejeção do Ventrículo Esquerdo (Feve) (p=0,022) e necessitaram de mais tempo para o início do tratamento antibiótico para endocardite (p < 0,001) quando comparadas àquelas com culturas positivas. Não houve diferença estatisticamente significante entre os grupos na letalidade intra-hospitalar e na sobrevida após alta hospitalar. Verificou-se que a presença de diabetes mellitus (p=0,009) ou sepse grave na admissão (p=0,01) esteve independentemente associada ao óbito intra-hospitalar entre as endocardites com culturas negativas. Dez casos de endocardite por Bartonella spp. (frequência 19,6% [IC95%: 9,8 - 33,1]) e quatro casos de endocardite por Coxiella burnetii (frequência 7,8% [IC95%: 2,2 - 18,9]) foram diagnosticados dentre os 51 episódios de endocardite com culturas negativas. As endocardites por Bartonella spp. apresentavam menor Feve (p=0,025), associação com a identificação de cocobacilo Gram-negativo no exame histológico da valva cardíaca (p=0,001) e presença de gato no domicílio (p=0,001). Conclusões: Bartonella spp. e Coxiella burnetii foram as etiologias de quase um terço (27,5%) das endocardites comunitárias com culturas negativas. A presença de gato no domicílio, Feve <= 45%, e a identificação de cocobacilo Gramnegativo no exame histológico da valva cardíaca em pacientes com endocardite com culturas negativas parecem estar associadas à infecção por Bartonella spp. O exame histológico da valva cardíaca permitiu a identificação morfológica do micro-organismo na maioria dos casos, mesmo quando as hemoculturas estavam negativas. Não se observou diferença na letalidade intra-hospitalar e na sobrevida em longo prazo entre os dois grupos. A presença de diabetes mellitus ou sepse grave à admissão associou-se ao óbito hospitalar nas endocardites com culturas negativas / Infective endocarditis is associated with high morbidity and lethality. Early diagnosis and recognition of the specific etiology can contribute to successful antibiotic treatment. However, approximately one-fourth of endocarditis cases remain without an etiologic diagnosis. This study aimed to identify the frequency of endocarditis caused by Bartonella spp. and Coxiella burnetii among cases of community-acquired culture-negative endocarditis and to also assess risk factors for such infections. As a secondary objective, the clinical, laboratory and prognostic features of community-acquired endocarditis were compared. Factors related to the in-hospital lethality of culture-negative endocarditis were also assessed. Between January 2004 and January 2009, 369 consecutive cases of endocarditis were investigated in patients attending the no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Cases occurring in adults, those classified by the modified Duke criteria as \"defined endocarditis\" and community-acquired cases were studied. In total, 221 cases of endocarditis comprising 170 culture-positive and 51 culturenegative cases were included. For the culture-negative cases, serology (indirect immunofluorescence reaction) and histopathological analyses for Bartonella spp. and Coxiella burnetii were performed. Cases were considered positive for Bartonella henselae or Bartonella quintana with IgG titers >= 800 and for Coxiella burnetii with antiphase I IgG titers > 800. Histopathological studies of the cardiac valves were capable of morphologically identifying the etiology in 87% of the culture-negative endocarditis cases, whereas the Gram stain was only positive in 10% of cases using fresh tissue. Culture-negative endocarditis patients presented a greater frequency of dyspnea on admission (p=0.001), lower C-reactive protein levels (p=0.009), and a lower left ventricular ejection fraction (LVEF) (p=0.022), and they required more time to start antibiotic therapy (p < 0.001) when compared with culture-positive patients. There was no statistically significant difference between the two groups regarding in-hospital lethality or survival after hospital discharge. Diabetes mellitus (p=0.01) or severe sepsis on admission (p=0.01) were independently associated with in-hospital death for culture-negative endocarditis. Ten cases of endocarditis caused by Bartonella spp. (frequency 19.6% [IC95%: 9.8 - 33.1]) and 4 caused by Coxiella burnetii (frequency 7.8% [IC95%: 2.2 - 18.9]) were diagnosed among the 51 cases of culture-negative endocarditis. Endocarditis caused by Bartonella spp. was associated with lower LVEF values (p=0.025), the identification of Gram-negative coccobacilli in cardiac valve histology (p=0.001) and the presence of a cat in the patient\'s residence (p=0.001). Conclusions: Bartonella spp. and Coxiella burnetii were the causative etiology of almost one-third (27.5%) of the community-acquired cases of culture-negative endocarditis. The presence of a cat in the patient\'s residence, a LVEF <= 45% and the identification of Gram-negative coccobacilli in the histological examination of the cardiac valve in patients with culturenegative endocarditis appear to be associated with Bartonella spp. as the causative etiology. Histological examination of the cardiac valves allowed for morphological identification of the causative microorganism in the majority of cases, even when blood cultures were negative. There was no difference in in-hospital lethality or long-term survival between the two groups. The presence of diabetes mellitus or severe sepsis at admission was associated with in-hospital death in cases of culture-negative endocarditis

The functional compartmentalization underlying neuronal polarity makes tightly regulated intracellular transport between the cell body, axons, and dendrites essential for proper development and homeostatic maintenance. Disruptions to neuronal trafficking are a major cause of neurodegenerative disease. Pathogenic variants in the microtubule motor protein KIF1A cause KIF1A Associated Neurological Disorder (KAND), a spectrum of rare neurodegenerative conditions. KAND is clinically and genetically heterogeneous, with a broad phenotypic spectrum and over a hundred pathogenic variants identified. KAND is poorly understood at both the clinical and molecular level, and there is currently no treatment. This work characterizes the natural history of KAND and describes a novel heuristic severity score. This severity score is then used to show how the location of pathogenic missense variants within the KIF1A motor domain correlates with disease severity, providing evidence the clinical phenotypic heterogeneity in KAND reflects and parallels the molecular phenotypes. Insights from the neuropathology of deceased KAND patients is used to focus a histopathologic assessment of the C3-Kif1aLgdg mouse model. C3-Kif1aLgdg/Lgdg mice have a cerebellar axonal torpedo phenotype, paralleling some of the pathological changes seen in the patients. Phenotypically, the C3-Kif1aLgdg mice were found to recapitulate some of the symptoms seen in patients including progressive spasticity and gait abnormalities associated with hind limb paralysis. To model the disease at a cellular level, iPSCs were derived from affected individuals and successfully used to generate neural stem cells and neurons. These patient-derived neurons were found to have increased markers of protein aggregates, a cellular phenotype that can be used to test potential treatments. Taken together, these studies provide foundational knowledge for future therapeutic development.