Bromodominios citoplasmáticos y acetilación de proteínas no nucleares en Trypanosoma cruzi

Trypanosoma cruzi es un protozoo flagelado y el agente etiológico de la enfermedad de Chagas. Tiene un ciclo de vida complejo que alterna entre dos huéspedes y por lo menos tres estadios de desarrollo diferentes. Este parásito presenta características únicas que lo hacen un interesante modelo para el estudio de diversas problemáticas de las células eucariotas. El bromodominio es un dominio proteico de unión a lisinas acetiladas, descripto originariamente en proteínas de unión a histonas acetiladas. Este dominio volutivamente conservado se encuentra comúnmente en proteínas nucleares que cumplen funciones relacionadas con la regulación de la estructura de la cromatina y la activación transcripcional. La capacidad única del bromodominio de reconocer lisinas acetiladas se relaciona con un nuevo mecanismo de regulación de las interacciones proteína-proteína vía acetilación de lisinas, el cual tiene amplias consecuencias en variados procesos celulares. En el genoma de Trypanosoma cruzi están presentes seis secuencias codificantes para proteínas con bromodominios. Nos propusimos caracterizar una de ellas, denominada Factor con Bromodominio 3 (TcBDF3), y evaluar su expresión en el parásito, su localización subcelular, su capacidad de interaccionar con sustratos acetilados y su rol en la biología de los tripanosomas. TcBDF3 se expresa en todos los estadios del ciclo de vida, presentando una localización atípica. En epimastigotes y amastigotes se encuentra en el citoplasma, flagelo y bolsillo flagelar mientras que en tripomastigotes solo en el flagelo. Pudimos determinar que este bromodominio es capaz de interaccionar con la α-tubulina acetilada presente en el citoesqueleto y flagelo de T. cruzi. Además, esta unión perece ser específica ya que no es capaz de reconocer histonas acetiladas. La sobre-expresión de una versión truncada de TcBDF3 hace que se pierda la localización flagelar y disminuye la capacidad de los epimastigotes de diferenciarse a tripomastigotes, proceso denominado metaciclogénesis. Al sobre-expresar de manera inducible una versión salvaje y una doble mutante puntual de TcBDF3 observamos nuevamente una disminución en la tasa de metaciclogénesis y efectos en las tasas de infección in vitro (esta doble mutante no posee la capacidad de unir α-tubulina acetilada). Estos resultados sugieren que este bromodominio es esencial para Trypanosoma cruzi y jugaría un papel importante en el proceso de diferenciación e infección. Finalmente, ensayamos distintos inhibidores de bromodominios comerciales sobre epimastigotes de T. cruzi y determinamos la capacidad de uno de ellos de unirse a TcBDF3 recombinante. Los resultados obtenidos durante este trabajo de tesis nos permiten proponer que TcBDF3 es esencial para el crecimiento y diferenciación de T. cruzi y que podría ser un blanco interesante para el desarrollo de nuevas drogas tripanosidas. Por otro lado, se abren nuevos interrogantes sobre el rol de la acetilación en la dinámica del citoesqueleto y como los bromodominios pueden participar en diversos mecanismos de regulación tanto dentro como fuera del núcleo.Fil: Alonso, Victoria Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina

Reencuadrar la obra : Sobre una práctica curatorial en torno a Juan Batlle Planas

En el presente escrito proponemos indagar en la práctica curatorial como una estrategia que tensiona los relatos desplegados por la historia del arte, particularmente, en torno a la obra de Juan Batlle Planas. Con frecuencia, la crítica y la historia del arte han señalado la pertenencia de la obra de Batlle Planas al estilo surrealista –o neorromántico, en la variante de Aldo Pellegrini–, al que se lo asocia en el carácter de precursor. Esta adscripción a un estilo histórico, que tiene el mérito de poner aquello reconocido como “surrealismo” argentino en pie de igualdad con las producciones canónicas del centro, descuida, no obstante, la complejidad del escenario cultural en el que operó Batlle Planas y su relación con las tramas particulares que adoptaron en Buenos Aires los procesos de transmisión de saberes y la experiencia de la técnica y la cultura urbana entre 1920 y 1960. A partir de una investigación realizada en el marco de la exposición Visiones ensambladas. Reencuadres a la obra de Batlle Planas, destacamos en este trabajo la importancia de proponer claves de ingreso alternativas a la obra del artista recomponiendo el entramado de saberes y consumos culturales, novedades y permanencias que articulan su producción.Facultad de Bellas Arte

Consumo de cigarrillo en la facultad de odontología de la universidad de antioquia y factores relacionados : Medellín, 2012

ABSTRACT: The goal of this study was to determine the frequency of cigarette smoking among staff from Universidad de Antioquia School of Dentistry and its related factors. Methods: cross-sectional study by means of a self-completion survey administered to professors, students, and employees. Variables: sociodemographic conditions, characteristics of the habit of smoking, weight and height (BMI), and relations with co-workers and classmates. Regarding smoking cessation, prevalence (P: current use) and experience (E: current/past use) were considered. The description of variables was done separately for women (W) and men (M). The association of experience and prevalence to sex, physical activity, and BMI was studied through logistic regression, calculating crude and adjusted Odds Ratio (ORc and ORa, respectively), with 95% confidence intervals (95% CI). Results: sex was significantly associated with smoking, being higher in men (P: ORa 5.34; IC95% 2.73-10.45 and E: ORa 2.93; IC95% 2.08-4.14). Physical activity also had statistically significant association to prevalence (ORa 5.78; 95% 2.02-16.53). Nearly a quarter of men and 8% of women have considered smoking sometime in their lives (p < 0.0001). In a greater proportion, the surveyed population reported that their co-workers or classmates smoke near them (M: 25%, W: 16%, p = 0,007). More than 75% of smokers of both sexes consider the possibility of quitting the habit, or have tried to do so. Conclusions: the habit of smoking showed differences in terms of sociodemographic factors. Promotion and prevention strategies are needed to encourage healthier lifestyles. Keywords: smoking, epidemiology, lifestyle, cross-sectional studies.RESUMEN: El objetivo del presente trabajo consistió en determinar la frecuencia del consumo de cigarrillo en el personal de la Facultad de Odontología de la Universidad de Antioquia, así como sus factores relacionados. Métodos: estudio transversal mediante encuesta autodiligenciada a docentes, estudiantes y empleados. Variables: sociodemográficas, características del hábito de fumar, peso y talla (IMC), y relaciones de convivencia. Con respecto al hábito de fumar, se tuvieron en cuenta la prevalencia (P: consumo actual), y la experiencia (E: consumo actual/pasado). Se realizó una descripción de las variables en forma separada para hombres (H) y mujeres (M). Se estudió la asociación entre la experiencia y la prevalencia con el sexo, la actividad física e IMC por medio de regresión logística, calculando Odds Ratio crudas (ORc) y ajustadas (ORa), con sus intervalos de confianza al 95% (IC95%). Resultados: el sexo se asoció significativamente con el consumo de cigarrillo, el cual fue mayor en los hombres (P: ORa 5,34; IC95% 2,73- 10,45 y E: ORa 2,93; IC95% 2,08- 4,14). La actividad física también tuvo asociación estadísticamente significativa para el caso de la variable prevalencia (ORa 5,78; IC95% 2,02- 16,53). Casi una cuarta parte de los hombres y un 8% de las mujeres han considerado fumar en alguna vez en la vida (p<0,0001). En mayor proporción, la población encuestada reportó que sus compañeros de trabajo o estudio fuman cerca de ellos (H: 25%, M: 16%, p=0,007). Más del 75% de los fumadores de ambos sexos piensan dejar el hábito de fumar, o han intentado hacerlo. Conclusiones: se encontraron diferencias en el hábito de fumar según factores sociodemográficos. Se requieren estrategias de promoción y prevención que conlleven a estilos de vida saludables. Palabras clave: hábito de fumar, epidemiología, estilo de vida, estudios transversales

The COVID-19 Sentinel Schools Network of Catalonia (CSSNC) project : Associated factors to prevalence and incidence of SARS-CoV-2 infection in educational settings during the 2020-2021 academic year

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools

Impact of regulated and emerging pollutants and microplastics in marine ecosystems (IMPACTA project)

Marine ecosystems are nowadays subjected to a massive input of synthetic chemicals from everywhere. Unfortunately only a small portion of them is being monitored, and it is necessary to identify which pollutants can produce adverse impacts in the marine environment. IMPACTA project (CTM2013-48194-C3) is characterizing the distribution of regulated and emerging contaminants and microplastics in marine sediments, and evaluating the biological effects that they can cause (sing sublethal embryotoxicity tests, endocrine disruption and biomarkers). Sensitive and selective analytical methods are being developed and validated for pharmaceuticals, perfluorinated compounds, organophosphorus pesticides, triazines, personal care products, nonylphenols and alkylated PAHs in sediments. Thus, relevant pollutants present in coastal and offshore areas will be identified. Furthermore potential toxic effects of the contaminants present in coastal sediments are being assessed through embryotoxicity bioassays and also the biological effects on different marine species as a consequence of their exposition to specific compounds. Another relevant contribution of this project will be the assessment of the impact of micro-plastics, first time in the Spanish coastal areas. Their potential toxic effects and their role in the transference of pollutants in the marine environment are being assessed. The concentration and composition of microplastics in sediments and demersal fish stomachs are being characterized, and their potential biological effects on marine invertebrates are also being investigated

Monitoring of SARS-CoV-2 seroprevalence among primary healthcare patients in the Barcelona Metropolitan Area: the SeroCAP sentinel network protocol

Introduction SARS-CoV-2 seroprevalence studies are currently being recommended and implemented in many countries. Forming part of the COVID-19 monitoring and evaluation plan of the Catalan Government Health Department, our network aims to initiate a primary healthcare sentinel monitoring system as a surrogate of SARS-CoV-2 exposure in the Barcelona Metropolitan Area. Methods and analysis The seroCAP is a serial cross-sectional study, which will be performed in the Barcelona Metropolitan Area to estimate antibodies against SARS-CoV-2. From February 2021 to March 2022, the detection of serum IgG antibodies against SARS-CoV-2 trimeric spike protein will be performed on a monthly basis in blood samples collected for diverse clinical purposes in three reference hospitals from the three Barcelona healthcare areas (BCN areas). The samples (n=2588/month) will be from patients attended by 30 primary healthcare teams at 30 basic healthcare areas (BHA). A lab software algorithm will systematically select the samples by age and sex. Seroprevalence will be estimated and monitored by age, sex, BCN area and BHA. Descriptive and cluster analysis of the characteristics and distribution of SARS-CoV-2 infections will be performed. Sociodemographic, socioeconomic and morbidity-associated factors will be determined using logistic regression. We will explore the association between seroprevalence, SARS-CoV-2 confirmed cases and the implemented measures using interrupted time series analysis. Ethics and dissemination Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina ethics committee. An informed consent is not required regarding the approval of the secondary use of biological samples within the framework of the COVID-19 pandemic. A report will be generated quarterly. The final analysis, conclusions and recommendations will be shared with the stakeholders and communicated to the general public. Manuscripts resulting from the network will be submitted for publication in peer-reviewed journals

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis Due to Behçet's Disease: National Multicenter Study of 177 Cases

Objective: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). Methods: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. Results: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). Conclusion: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up

Development of an activity disease score in patients with uveitis (UVEDAI)

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases

Recurrent dissemination of SARS-CoV-2 through the Uruguayan–Brazilian border

Uruguay is one of the few countries in the Americas that successfully contained the coronavirus disease 19 (COVID-19) epidemic during the first half of 2020. Nevertheless, the intensive human mobility across the dry border with Brazil is a major challenge for public health authorities. We aimed to investigate the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains detected in Uruguayan localities bordering Brazil as well as to measure the viral flux across this ∼1,100 km uninterrupted dry frontier. Using complete SARS-CoV-2 genomes from the Uruguayan–Brazilian bordering region and phylogeographic analyses, we inferred the virus dissemination frequency between Brazil and Uruguay and characterized local outbreak dynamics during the first months (May–July) of the pandemic. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 Brazilian lineages B.1.1.28 and B.1.1.33 into Uruguayan localities at the bordering region. The most probable sources of viral strains introduced to Uruguay were the Southeast Brazilian region and the state of Rio Grande do Sul. Some of the viral strains introduced in Uruguayan border localities between early May and mid-July were able to locally spread and originated the first outbreaks detected outside the metropolitan region. The viral lineages responsible for Uruguayan urban outbreaks were defined by a set of between four and 11 mutations (synonymous and non-synonymous) with respect to the ancestral B.1.1.28 and B.1.1.33 viruses that arose in Brazil, supporting the notion of a rapid genetic differentiation between SARS-CoV-2 subpopulations spreading in South America. Although Uruguayan borders have remained essentially closed to non-Uruguayan citizens, the inevitable flow of people across the dry border with Brazil allowed the repeated entry of the virus into Uruguay and the subsequent emergence of local outbreaks in Uruguayan border localities. Implementation of coordinated bi-national surveillance systems is crucial to achieve an efficient control of the SARS-CoV-2 spread across this kind of highly permeable borderland regions around the world