Sua história natural e o real risco à função renal foram pouco estudados. Objetivo: Avaliar o impacto do cálculo ureteral silencioso sobre a função renal antes a após o tratamento, procurando por fatores preditivos de uma melhor evolução. Material e Método: O cálculo ureteral silencioso foi definido como aquele em que o paciente não apresentava nenhum sintoma subjetivo ou objetivo a ele relacionado. Os pacientes com cálculo ureteral silencioso foram prospectivamente incluídos no estudo, sendo avaliados com 99mTc-DMSA, creatinina sérica (Cr), ritmo de filtração glomerular (RFG) e ultrassonografia (USG) no pré-tratamento, três e 12 meses após o mesmo. Pacientes que receberam tratamento fora de nossa instituição e aqueles com avaliação perioperatória incompleta foram excluídos. A análise estatística incluiu os testes de ANOVA, Qui-quadrado/Fisher, e regressão logística/múltipla. O nível de significância foi estabelecido em p<0,05. Resultados: Entre jan/2006 e jan/2014, 26 pacientes com cálculo ureteral silencioso, correspondendo a 2,1% de todos os cálculos ureterais tratados, preencheram os critérios de inclusão do estudo. Treze pacientes eram do sexo feminino, com idade média de 59,3 ± 11,3 anos. O diagnóstico do cálculo foi relacionado a uma causa urológica em 14 (53,8%) casos. O diâmetro e densidade média dos cálculos era de 11,8 ± 2,8 mm e 1201 ± 272 UH, respectivamente. Apenas dois pacientes não apresentavam hidronefrose ao USG inicial e a espessura média do parênquima renal era 10,7 ± 4,1 mm. Os valores médios pré-operatórios de Cr, RFG e 99mTc-DMSA foram 1,24 ± 0.87 mg/dl, 72,5 ± 25.2 mL/min e 33,4 ± 16,7%, respectivamente. Vinte (77%) pacientes apresentavam 99mTc-DMSA < 45% no exame inicial. Regressão múltipla revelou que idade (p=0,041) e espessura do parênquima renal (p=0,001) predizem o valor do 99mTc-DMSA inicial. Quando comparados com os valores pré-operatórios, a Cr (p=0,89), o RFG (p=0,48) e a função renal ao 99mTc-DMSA (p=0,19) permaneceram inalterados com três e 12 meses após o tratamento. A hidronefrose apresentou melhora três meses após o tratamento (p < 0,01), mas manteve-se inalterada no período entre três e 12 meses (p=0,06). Nenhuma variável pré-operatória foi capaz de prever uma variação > 5% do 99mTc-DMSA entre pré e pós-operatório, sendo que o tamanho do cálculo (p=0,12) e tempo para tratamento (p=0,15) tiveram influência marginal. Conclusão: O cálculo ureteral silencioso está associado à diminuição da função renal e algum grau de hidronefrose já ao diagnóstico. Idade, espessura do parênquima renal e grau de hidronefrose predizem o valor inicial do 99mTc-DMSA. Enquanto a hidronefrose regride após a remoção do calculo, a função renal se mantém inalterada. Nenhum fator conseguiu predizer significativamente a evolução da função renal ao 99mTc-DMSA doze meses após o tratamento / Introduction: Ureteral stones may be asymptomatic in 0.3-5.3% of patients. The natural history and the disease influence on renal function have been poorly studied. Objective: to evaluate the impact of silent ureteral stone on renal function before and after treatment, searching for predictive factor of better outcomes. Material and Method: A ureteral stone was defined as silent if the patient had no subjective/objective symptoms related to the calculus. Patients with a silent ureteral stone were prospectively enrolled in the study. Patients were evaluated with 99mTc-DMSA scintigraphy, serum creatinine (Cr), Cr clearance (CrCl) and ultrasound (USG) pre and post-operatively on months three and 12. Patients treated outside our institution or with incomplete perioperative evaluation were excluded. ANOVA, Chi-square/Fisher test, and regression analysis were used. Significance was set at p < 0.05. Results: Between Jan/06-Jan/14, 26 patients with silent ureteral stones met our inclusion criteria, comprising 2.1% of all ureteral stones treated at our institution. Half of patients were female, mean age was 59.3 ± 11.3 years-old. Stone diagnosis was related to a urological cause in 14 (53.8%) cases. Mean stone diameter and density were 11.8 ± 2.8 mm and 1201 ± 272 HU, respectively. Only two patients had no hydronephrosis at initial USG evaluation and mean renal parenchyma thickness was 10.7 ± 4.1mm. Mean preoperative Cr, CrCl and 99mTc-DMSA were 1.24 ± 0.87 mg/dL, 72.5 ± 25.2 mL/min and 33.4 ± 16.7%, respectively. Twenty (77%) patients had 99mTc-DMSA < 45% at initial examination. Multiple regression revealed age (p=0.041) and renal parenchyma thickness (p=0.001) to predict initial 99mTc-DMSA. When compared to preoperative values, Cr (p=0.89), CrCl (p=0.48) and 99mTc-DMSA (p=0.19) remained unaltered three and 12 months postoperatively. Hydronephrosis improved from before to three months after treatment (p < 0.01), but remained unchanged from three to 12 months (p=0.06). No preoperative variable was able to predict a > 5% variation on 99mTc-DMSA from pre to postoperative periods, though stone size (p=0.12) and time to treatment (p=0.15) had a marginal influence. Conclusion: Silent ureteral stones are associated with decreased renal function and hydronephrosis already at diagnosis. Age, renal parenchyma thickness and degree of hydronephrosis predict initial 99mTc-DMSA. Hydronephrosis tends to diminish after stone removal, while renal function remains stable. No preoperative factor significantly predicted renal function progression twelve months postoperatively

Introduction. La neurocysticercosis (NCC) est l'un des maladies helminthiques les plus courantes du SNC et elle cause de l'épilepsie symptomatique dans les régions pauvres. Il existe peu d'études communautaires sur cette zoonose et leurs comorbidités comme l'épilepsie et la NCC. Méthodologie. Dans la région nord du Pérou, trois études sur la communauté et une révision systématique ont été développés dont les objectifs étaient les suivants: a) évaluer la prévalence de la NCC asymptomatique, b) la prévalence de l'épilepsie associée à la cysticercose, c) la détermination de l'exposition à la cysticercose d) développer une intervention communautaire pour interrompre la transmission de la cysticercose. Résultats. 256 patients asymptomatiques qui avaient une tomodensitométrie (T) sans contraste, 48 (18%) avaient la NCC calcifiés. La prévalence de l'épilepsie trouvée était de 17.25 / 1000 habitants et la proportion de NCC en personnes atteintes d'épilepsie était de 39% (109/282). Le Western Blot (EITB-LLGP) pour la cysticercose a été positive dans le 40% des personnes atteintes d'épilepsie, et dans le 36,9% de la population générale. L'association entre la cysticercose et l'épilepsie avait un OR de 2,7 (95% CI 2.1 – 3.6, p <0,001). Le traitement massif avec niclosamide chez l'homme (n = 3), et plus la vaccination de la population porcine a été mis en oeuvre dans 107 communautés rurales de Tumbes. Aucun porc infecté avec la cysticercose n’a été trouvé en 105 des 107 communautés. Conclusions. (1) La NCC est un facteur contributeur de l'épilepsie, (2) La transmission de T. solium peut être réduite à échelle régionale. / Backgrounds. Neurocysticercosis is a parasitic infection of the brain and a common cause of epilepsy in poor regions. There are scarce community-based studies about its comorbidities as epilepsy and neurocysticercosis. Methods. In the northern region of Peru, we performed three community based-studies and one systematic review a) to assess the prevalence of asymptomatic NCC, b) the prevalence of epilepsy and epileptic seizures and NCC c) seroprevalence of cysticercosis (EITB-LLGP) and d) to perform a community intervention to interrupt the Taenia solium transmission. Results. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC. Lifetime prevalence of epilepsy was 17.25/1000, the proportion of NCC in people with epilepsy was 39% (109/282), and the seroprevalence of EITB-LLGP in individuals with epilepsy was 40% and between 23.4 to 36.9% in the general population. The association between CC and epilepsy had a OR of 2.7 (95% CI 2.1-3.6, p <0.001). Three rounds of mass treatment with niclosamida in humans and mass treatment and vaccination in pigs was implemented in 107 rural communities (n=81,170 people). No infected pigs with cysticercosis were found in 105 of 107 communities. Conclusion. NCC is a strong contributor of epilepsy and epileptic seizures. We showed that transmission of Taenia solium infection was interrupted on a regional scale in endemic regions in Peru / Introducción. La neurocisticercosis (NCC) es una de las enfermedades helmínticas más frecuentes del SNC y causa de epilepsia sintomática en regiones pobres. Hay escasos estudios basados en comunidad sobre esta zoonosis y sus comorbilidades la epilepsia y la NCC. Metodología. Se desarrollaron en la Región Norte del Perú tres estudios basados en la comunidad, y una revisión sistemática cuyos objetivos fueron: a) evaluar la prevalencia de NCC asintomática, b) la prevalencia de epilepsia asociada a cisticercosis, c) determinación de la exposición a cisticercosis y d) desarrollar una intervención comunitaria que interrumpa la transmisión de cisticercosis. Resultados. De 256 pacientes asintomáticos que tuvieron una tomografía axial computarizada (TAC) cerebral sin contraste, 48 (18%) tuvo una NCC calcificada. La prevalencia de epilepsia encontrada fue de 17.25/1000 habitantes y la proporción de NCC en personas con epilepsia fue de 39% (109/282). El Western Blot (EITB-LLGP) para cisticercosis fue positivo en el 40% de los individuos con epilepsia, y en el 36.9% de la población general. La asociación entre cisticercosis y epilepsia tuvo un OR de 2.7 (95% CI 2.1-3.6, p <0.001). El tratamiento masivo con niclosamida en humanos (n=3), y población porcina más vacunación fue implementada en 107 comunidades rurales de Tumbes; en 105 de 107 no hubo nuevos cerdos infectados con cisticercosis. Conclusiones. (1) La NCC es un factor contribuidor de epilepsia, (2) Se puede cortar la trasmisión de T. solium a escala regional.

Despite the advances made since the advent of germ theory, infectious diseases still wreak havoc on human societies, not only affecting us directly but impacting the crops and livestock upon which we rely. Infectious diseases also have dramatic effects on wildlife ecology. Therefore research into infectious diseases could not only directly lead to the improvement and saving of human lives, but aid in food security and the conservation of many wildlife species. Of vital importance in understanding the ecology of infectious diseases are the mechanisms by which they persist in host populations. One possible mechanism is vertical transmission: the transmission of a pathogen from a parent to its offspring as a result of the process of host reproduction. Another possible mechanism is inapparant infections, where an infected host does not display symptoms. Focusing on dengue fever and the Plodia interpunctella granulovirus laboratory system, this PhD thesis looks at the role these two mechanisms play on the persistence of two viral infections and their ecology. Regarding the Plodia interpunctella granulovirus (PiGV) low host food quality led to greater detection of vertically transmitted inapparant PiGV, but did not lead to its activation to an apparent form. Host inbreeding did not lead to vertically transmitted inapparant PiGV’s activation, nor had an effect on its vertical transmission. The vertical infection rate of PiGV was very low. I would therefore suggest that it may be better to use an insect virus system with a higher rate of vertical infection in future research into vertically transmitting inapparent infections. Regarding dengue virus I conclude that vertical transmission is not likely to play a role in the persistence of this virus. However modelling work found that inapparent infections could provide dengue viruses with a means of persistence and should be subject to further research.

En anthropologie médico-légale la détermination du sexe, l'estimation de l'âge au décès et l'estimation de la stature sont des paramètres essentiels à la constitution du profil biologique d'un individu à partir de restes osseux. Toutefois uniquement à partir de ces trois paramètres les interprétations sont limitées, plusieurs individus peuvent partager un même profil. L'introduction et l'observation d'autres paramètres, comme les variations anatomiques, peuvent être un atout dans l'établissement du profil biologique le plus singulier et complet possible afin de ne correspondre qu'à un nombre très restreint d'individus voire à un seul individu. En plus des variations anatomiques, l'observation des marqueurs de posture et des anomalies congénitales asymptomatiques peut aussi se révéler être pertinente. Ils ont été regroupés sous le terme de Variations Osseuses Asymptomatiques (VOA). Cent-neuf VOA ont été recensées sur le squelette postcrânien et 82 ont été étudiées à partir de 1300 individus provenant de trois populations différentes : une population contemporaine (imagerie médicale), une population ostéologique de référence et une population ostéoarchéologique. Pour chacune des VOA, la fréquence a été obtenue à partir des trois échantillons puis une fréquence en fonction du sexe, de l'âge et de la latéralité a été calculée. Une iconographie claire de chaque VOA a été obtenue. L'intérêt final est de ne sélectionner que les VOA ayant une fréquence inférieure à 10 % et facilement observables afin d'aider à l'identification en complétant le profil biologique, et ceci à partir d'une méthode basée sur la comparaison de données ante et post-mortem. / In forensic anthropology, determination of sex, estimation of age at death and estimation of stature are essential parameters for constituting the biological profile of an individual from bone remains. However, using only three parameters limits interpretation, several individuals could share the same profile. The introduction and observation of others parameters, particularly anatomical variations, could help establish a more complete and specific biological profile to correspond to a restricted number of individuals or to a unique individual. In addition to anatomical variations, postural markers and congenital anomalies can be useful for identification purposes. These 3 elements are regrouped under the term Asymptomatic Osseous Variation (AOV). 109 AOVs were found on the postcranial skeleton and 82 were studied on 1300 individuals from three different populations: a contemporary population (medical imaging), an osteological collection of reference and an osteoarcheological population. Frequencies were obtained from the three samples for each AOV, and frequencies according to sex, age and laterality were calculated. A clear iconography of each AOV was obtained. This data enabled the classification of the AOVs according to 5groups of frequencies, ranging from very rare to very frequent. The AOVs were also classified according to their liaison with sex, age and laterality. The final goal is to select only AOVs with a frequency inferior to 10% (qualified as rare), that are easily observable, to be useful for establishing the biological profile and help identify the individual, using a method based on ante and post-mortem data comparison.

Visceral leishmaniasis is endemic in many Brazilian states, including Sergipe. Through a cross-sectional study done with relatives of patients with visceral leishmaniasis, we determined the frequency of asymptomatic infection by Leishmania chagasi using Montenegro skin test and/or Enzyme Linked Immunosorbent Assay (ELISA). Questionnaire containing socio-demographic data, presence of signs and symptoms, physical examination of 109 subjects were analyzed. Environmental factors such as the presence of dog, chicken and wood in the residence were also investigated. Finally, the levels of cytokines Tumor Necrosis Factor (TNF)-α, Transforming Growth Factor (TGF)-β and Interleukin (IL)-1, IL-6, IL-8, IL-10 and IL-12 were measured in 59 of these individuals. The frequency of positivity was detected in 51.8% of participants, being higher in males (61.9%). Positive testes were also more common in people over 14 years (79.7%). All positive individuals were considered asymptomatic and did not return to the hospital with complaints until the end of the study, suggesting that did not progress to other clinical forms. There was no difference between the origin: capital or the state, but more positive cases occurred at the capital, confirming the growing urbanization of the disease. Environmental factors was statistically significant when analyzed presence of dog and waste wood together (p <0.05). TGF-β showed a significant difference in favor of the negative individuals (p = 0.002), while IL-10 and IL-12 were higher in people with positive tests (p = 0.024 and 0.038). Control measures should be aimed to the population of our state, who is highly exposed to the parasite. / A leishmaniose visceral é uma doença que possui amplo espectro clínico, variando desde infecção clássica a formas subclínica e assintomática. Através de um estudo transversal feito com familiares de pacientes com leishmaniose visceral, determinamos a frequência de infecção assintomática por Leishmania infantum chagasi, utilizando Intradermorreação de Montenegro e/ou sorologia por Enzyme Linked Immunosorbent Assay (ELISA). Questionário contendo dados sócio-demográficos, presença de sinais e sintomas, exame físico de 109 indivíduos foram analisados. Fatores ambientais como presença de cachorro, galinheiro e restos de madeira no domicílio também foram investigados. Níveis do Fator de Necrose Tumoral (TNF-α), Fator de Transformação do Crescimento (TGF-β) e as interleucinas IL-1, IL-6, IL-8, IL-10 e IL-12 foram dosados em 59 destes indivíduos. A frequência de positivos foi detectada em 51,8% dos participantes, sendo maior no sexo masculino (61,9%). Testes com resultado positivo também foram mais frequentes em pessoas acima de 14 anos (79,7%). Todos os indivíduos positivos foram considerados assintomáticos e não retornaram ao serviço de saúde com queixas até o final da pesquisa, sugerindo que não evoluíram para outras formas clínicas. Não houve diferença entre o local de moradia: capital ou interior do Estado, porém mais casos positivos ocorreram na capital, confirmado a crescente urbanização da doença. Dentre os fatores ambientais ocorreu significância estatística quando analisamos presença de cachorro juntamente com restos de madeira (p<0,05). TGF-β mostrou diferença significativa em favor dos negativos (p=0,002), enquanto IL-10 e IL-12 foram maiores nos indivíduos com testes positivos (p= 0,024 e 0,038). Diante dos achados, verificamos que medidas de controle da disseminação da leishmania devem ser efetivadas e direcionadas à população do nosso Estado, uma vez que a exposição ao parasita ainda é muito alta, colocando-a em risco de desenvolver a doença.

The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide 'heterologous protection' from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an 'asymptomatic epitope'-based lipopeptide vaccine.

Urinvägsinfektioner (UVI) är ett vanligt hälsoproblem som drabbar miljontals människor. Den allvarligaste formen, akut pyelonefrit (APN) kan ge svåra komplikationer. Urinvägspatogena Escherichia coli (UPEC) som orsakar APN uttrycker P fimbrier som specifikt binder till glykosphingolipider på ytan av uroepitelceller. Det sätter igång en toll-like receptor 4 (TLR4) beroende men LPS-oberoende immunreaktion. Den roll som interferon beta (IFN-β) spelar vid bakterieinfektioner är inte helt klarlagd men studier som gjorts på IFN-β knockoutmöss visade på en ökad infektionsbenägenhet och svåra njursymptom vid infektion med UPEC. IFN-β uttrycket i uroepitelceller som svar på bakterieinfektion undersöktes. För att ta reda på om uttrycket är P fimbrieberoende infekterades humana A498 njurcarcinomceller med den P fimbrieförsedda pyelonefritstammen CFT073 eller den icke-virulenta asymtomatisk bakterieuristammen E. coli 83972 och inkuberades i 1,5 respektive 4 timmar. Som kontroll användes celler som enbart behandlats med PBS. Uttrycket av IFN-β analyserades med immunofluorescens (IF) och konfokalmikroskopi, samt med Western blot. Resultaten från konfokalmikroskopi visade att celler som exponerats för CFT073 under 4 timmar uttryckte mest IFN-β medan cellerna som utsatts för E. coli 83972 visade på ett omvänt förhållande. Western blot visade på högst uttryck i de E. coli 83972-behandlade cellerna. IFN-β uttrycktes i alla celler, inklusive kontrollcellerna, i någon utsträckning. Det kan betyda att IFN-β även induceras på någon alternativ väg och/eller att det uttrycks konstitutivt av njurepitelceller. / Urinary tract infections (UTI) are a common health concern and affect millions of people. The most severe form of UTI, acute pyelonephritis (APN) is associated with serious complications. Uropathogenic Escherichia coli (UPEC) that cause APN express P fimbriae which specifically bind to glycosphingolipid molecules on the surface of urothelial cells. This triggers a toll-like receptor 4 (TLR4) mediated but LPS-independent innate immune response. The role of interferon beta (IFN-β) in bacterial infections is not well known but experiments with IFN-β knockout mice have shown an increased susceptibility and severe kidney pathology when infected with UPEC. IFN-β induction in urothelial cells in response to bacterial infection was investigated. To find out whether this response is P fimbriae dependent, A498 human kidney carcinoma epithelial cells were exposed to the P fimbriated CFT073 pyelonephritis strain or the non-virulent E. coli 83972 asymptomatic bacteriuria strain and incubated for 1.5 and 4 hours. For control, cells were treated with PBS alone. The IFN-β expression was analysed using immunofluorescence (IF) and confocal microscopy, and Western blot. Confocal microscopy results showed that the response to bacteria was both time- and dose-dependent. The highest IFN-β expression was detected in cells exposed to CFT073 for 4 hours, while cells exposed to E. coli 83972 showed an inverse relationship. Western blot analysis revealed that the highest expression was in the E. coli 83972 stimulated cells. IFN-β was expressed in all cells to some degree, including control cells. This could imply that IFN-β is induced by some other means and/or is constitutively expressed by kidney epithelial cells.

Contexte : Les maladies valvulaires dégénératives (MVD) représentent la pathologie cardiaque acquise la plus fréquente chez le chien. Malgré une recherche active, à l’heure actuelle aucun traitement étudié ne s’est avéré efficace dans le traitement du stade asymptomatique de la condition. Le pimobendane est un nouvel agent inodilatateur, qui s’est montré prometteur dans le traitement des stades avancés des MVD, mais peu est connu sur ses effets hémodynamiques et son impact sur le volume de régurgitation dans les MVD naturelles asymptomatiques. Hypothèses : L’introduction du pimobendane réduit la fraction de régurgitation (FR) chez les chiens atteints de MVD asymptomatiques. Sujets étudiés : Vingt-quatre chiens de compagnie, appartenant à la clientèle du Centre Hospitalier Universitaire Vétérinaire (CHUV) de l’université de Montréal et affectés par une MVD de classe ISACHC 1b. Méthode: Étude prospective, contrôlée et conduite à l’aveugle. Les chiens ont été assignés à un groupe traitement (n=19) recevant du pimobendane (0,2-0,3 mg/Kg q12h) ou à un groupe contrôle (n=5). Les évaluations échocardiographiques ont été effectuées sur une période de 6 mois. Résultats : L’introduction du pimobendane n’a pas été associée à une diminution de la FR chez les chiens affectés par une MVD asymptomatique de classe ISACHC 1b au cours de l’étude (p=0,85). Une augmentation significative de la fraction d’éjection (80,8 +/- 1,42 vs. 69,0 +/- 2,76, p=0,0064) ainsi qu’une baisse du diamètre ventriculaire gauche télé systolique (p=0.011) ont été observées chez le groupe pimobendane au jour 30. Toutefois, cet effet sur la fonction systolique n’a pas persisté au cours des 6 mois d’évaluation. / Background: Mitral Valve disease (MVD) is the most common acquired cardiac affectation of the dog, and is therefore associated with an undeniable clinical and economical importance for veterinarians and pet owners. Despite active research, at this time no known treatment has been proven to delay the onset of congestive heart failure. Pimobendan is a novel inodilator that has shown promising results in the treatment of advanced MVD, but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring asymptomatic MVD. Hypothesis: Administration of pimobendan decreases the regurgitant fraction (RF) of dogs with asymptomatic MVD. Animals: Twenty-four client-owned dogs affected by ISACHC class Ib MVD. Methods: Prospective, blinded, controlled clinical trial. Dogs were assigned to a pimobendan (0.2-0.3 mg/Kg q12h) treatment group (n=19) or a control group (n=5). Echocardiographic evaluations were performed over a 6 month study period. Results: Administration of pimobendan to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (p=0.85). There was a significant increase in the ejection fraction of the pimobendan treated dogs at day (80.8 +/- 1.42 vs. 69.0 +/- 2.76, p=0.0064), and a decrease in systolic left ventricular diameter (p=0.011). However, this improvement in systolic function was not sustained over the 6 month trial period.

Introdução: As doenças cerebrovasculares constituem-se um sério problema de saúde, e dados sobre sua prevalência mundial são alarmantes. A doença aterosclerótica dos vasos cervicais é um importante fator etiológico de isquêmica cerebral, por mecanismos que envolvem fenômenos embólicos e hipofluxo cerebral. Enquanto o manejo dos pacientes com estenose carotídea sintomática geralmente requer procedimentos cruentos como a endarterectomia e a angioplatia com stent carotídeo, não estão bem definidos o espectro clínico e o manejo adequado dos pacientes com estenoses carotídeas ditas assintomáticas (sem evidência de evento cerebrovascular ipsilateral). Neste contexto, é possível que a presença de déficits cognitivos e as alterações estruturais e funcionais na ressonância magnética cerebral possam ser úteis para a estratificação e o manejo destes pacientes. Objetivos: constitui objetivo principal do presente estudo investigar associações entre biomarcadores de ressonância magnética e desempenho cognitivo, em sujeitos com estenose carotídea assintomática unilateral. Métodos: foram incluídos na pesquisa 13 voluntários, com diagnóstico de doença aterosclerótica assintomática unilateral com comprometimento >= 70% da luz do vaso, recrutados nos ambulatórios de neurologia e cirurgia vascular, do Hospital das Clínicas, da Faculdade de Medicina de Ribeirão Preto - FMRP/ USP. Participaram do grupo controle 13 voluntários, sem antecedentes de doenças cerebrovasculares. A avaliação neuropsicológica consistiu na aplicação do Subteste Dígitos (WAIS); Trail Making Test; Stroop Test; Teste das Figuras Complexas de Rey; provas de fluência verbal fonêmica e categoria semântica; e o Mini Exame do Estado Mental, edições 1 e 2. Para a composição da avaliação de neuroimagem por ressonância magnética, foram inclusas: (1) imagens FLAIR (fluid attenuated inversion recovery) para avaliação de carga de lesão de substância branca; (2) imagens de ASL (arterial spin labeling), ponderadas em perfusão sanguínea, para quantificação do fluxo sanguíneo cerebral; e (3) imagens baseadas no contraste BOLD (blood oxygenation level dependent), em repouso, para avaliação da conectividade funcional. Análises estatísticas foram realizadas pelo Stata 15.1, em que as variáveis foram testadas para normalidade usando o teste de normalidade de Shapiro-Wilk. O teste t de amostras independentes e o teste U de Mann-Whitney foram utilizados para analisar as diferenças entre os grupos. As diferenças hemisféricas na carga de WMH foram testadas pelo teste t pareado, ou Wilcoxon. Testes Chi-squared ou Teste Exato de Fisher foram utilizados na análise de variáveis categóricas. Os coeficientes decorrelação de Pearson ou Spearman foram utilizados para explorar correlações entre escores cognitivos, volume de substância branca, carga de WMH, CBF e conectividade funcional. Resultados: O volume de substância branca (SB) em pacientes com estenose carotídea assintomática mostrou-se marcadamente reduzido, enquanto hiperintensidade de sinal em SB esteve significativamente aumentada em relação a indivíduos controles (p < 0,01). O hemisfério ipsilateral à estenose assintomática grave apresentou carga mais expressiva de lesão em SB (p = 0,01). Neste contexto, a presença de estenose assintomática esteve independentemente associada à hiperintensidade de SB. Análises de CBF não revelaram diferenças entre os grupos clínicos e controle, embora o CBF tenha sido associado ao desempenho das funções cognitivas em todos os domínios avaliados por este estudo. Não foram identificadas diferenças de fluxo sanguíneo global em territórios das artérias cerebrais anterior, média e posterior, entre sujeitos com estenose de artéria carótida assintomática e controles. Pacientes apresentaram prejuízos de conectividade em redes cerebrais de repouso (RSBNs), especialmente frontotemporal, saliência e rede atencional dorsal, em relação aos controles (p-FDR < 0,01). A performance cognitiva de pacientes com estenose carotídea foi inferior ao grupo controle, para todas as medidas, com diferenças significativas em domínios mnemônicos, atencionais e funções executivas (p<0.05), estes relacionados com RSBNs. Conclusões: Nós identificamos anormalidades pré-clínicas no volume de SB, CBF, conectividade funcional e no desempenho cognitivo de pacientes com estenose carotídea assintomática. Biomarcadores de neuroimagem na RM, combinados à avaliação cognitiva têm um grande potencial para identificação de pacientes com estenose carotídea assintomática sob risco elevado de AVC e declínio cognitivo. / Background: Cerebrovascular diseases are an important health problem worldwide with high prevalence, mortality and morbidity. Among its etiological subtypes, atherosclerotic disease involving the carotid artery is strongly associated with ischemic stroke due to arterial embolism and hemodynamic compromise. The management of symptomatic carotid stenosis generally requires carotid endarterectomy or stenting. Nevertheless, the management of asymptomatic carotid stenosis and patient selection for these procedures is still largely debated. It is possible that the presence of cognitive impairment, alterations on functional and structural magnetic resonance imaging (MRI) biomarkers of cerebrovascular disease could help the stratification and management of these patients. Objetives: to investigate the association between MRI biomarker of cerebrovascular disease and cognitive function in patient with unilateral asymptomatic carotid stenosis. Methods: we evaluated 13 patients with unilateral carotid stenosis >= 70% recruited from a tertiary academic outpatient clinic in Brazil and 13 control subjects without carotid stenosis or history of cerebrovascular diseases paired by age and sex. The neuropsycological evaluation included the WAIS, Trail Making Test; Stroop Test; Rey complex figures test; verbal fluency and categorical semantic fluency; and the minimental state 1 and 2. The MRI evaluation included: (1) FLAIR evaluation of white matter (WM) burden; (2) ASL evaluation of cerebral blood flow (CBF); (3) resting-state BOLD for evaluation of functional connectivity. Statistical analyses were performed with the Stata 15.1 package. Normality of the distribution of the variables was assessed with the Shapiro-Wilk test. We also used the student t test, Mann-whytney test, Chi-squared test and Fisher exact test as appropriate for univariate analyses. Pearson and Spearman correlation coefficients were used to explore the correlations among cognitive performance scores, WM volume, burden of WM hyperintensities, CBF and brain functional connectivity. Results: the global WM volume was markedly reduced and the global WM hyperintensity was significantly increased within the ipsilateral hemisphere in patients with unilateral carotid stenosis, when compared to controls (p < 0,01). CBF evaluated by ASL was associated with cognitive function but it was not significantly different between patients and controls within the arterial territories of the major intracranial arteries. Patients with carotid stenosis showed marked compromise of the brain connectivity within the frontotemporal, attentional and salience networks when compared to controls (p-FDR < 0,01). The cognitive performance was inferior for patients with unilateral carotid stenosis compared to controls in several cognitivedomains including executive function, attention and mnemonic domains. Conclusions: patients with asymptomatic carotid stenosis have high frequency of pre-clinical abnormalities on structural and functional MRI biomarkers and cognitive impairment. Evaluation of cognitive function, structural and functional MRI biomarkers of cerebrovascular disease may have a role to improve patient stratification and selection for interventions among patients with unilateral carotid stenosis.

Estudos relacionados à malária autóctone em regiões de baixa transmissão no Brasil ganham cada vez mais relevância científica e epidemiológica, pois revelam a manutenção desse cenário em regiões de Mata Atlântica remanescente. No sudeste do Estado de São Paulo, a ocorrência de surtos no município de Juquitiba tem sido foco de pesquisas sobre a prevalência de Plasmodium na população, com registros de casos assintomáticos. Relatos de ocorrência da doença ou da presença de anticorpos antiplasmodiais em gestantes nessa região não haviam sido descritos anteriormente. Embora infecções por P. falciparum em gestantes tenham sido amplamente abordadas na literatura, a interação entre P. vivax e P. malariae com esta coorte imunodeprimida foi pouco explorada até o momento. Nesse estudo nós monitoramos trimestralmente a circulação de Plasmodium em gestantes atendidas em cinco Unidades de Saúde de Juquitiba. Para isso foi empregado o diagnóstico por gota espessa e metodologias moleculares sensíveis para detecção do parasito, além de ensaios imunológicos para avaliação de parâmetros imunes humorais. Desse modo, foram detectadas infecções por P. vivax e P. malariae em gestantes, incluindo casos assintomáticos. A alta prevalência de anticorpos IgG nesta população mostrou importante exposição das gestantes ao Plasmodium. Em regiões com perfil semelhante ao apresentado neste estudo, o diagnóstico de malária poderia ser indicado no seguimento pré-natal / Studies related to autochthonous malaria in low transmission areas in Brazil have acquired scientific and epidemiological relevance, since they suggest continued transmission in remaining Atlantic Forest regions. In the Southeast of São Paulo State, outbreaks in the municipality of Juquitiba has been focus of studies on the prevalence of Plasmodium in the population, with reports of asymptomatic cases. Data on the occurrence of the disease or presence of antiplasmodial antibodies in pregnant women in this region were not described previously. Although P. falciparum infections in pregnant women have been widely addressed in the literature, the interaction of P. vivax and P. malariae with this immunocompromised cohort were poorly explored to date. In this study, we monitored quarterly the circulation of Plasmodium in pregnant women in five health facilities in Juquitiba. For this purpose, we performed diagnosis by thick blood film and sensitive molecular protocols for parasite DNA detection, as well immunological assays in order to evaluate humoral immune parameters. Through these tools, it was possible to detect infections due to P. vivax and P. malariae in pregnant women, including asymptomatic cases. The high prevalence of IgG antibodies showed a significant exposure of this population to Plasmodium. In regions with a similar profile presented in this study, the diagnosis of malaria might be indicated in prenatal care