Yersinia Controls Type III Effector Delivery into Host Cells by Modulating Rho Activity

Yersinia pseudotuberculosis binds to β1 integrin receptors, and uses the type III secretion proteins YopB and YopD to introduce pores and to translocate Yop effectors directly into host cells. Y. pseudotuberculosis lacking effectors that inhibit Rho GTPases, YopE and YopT, have high pore forming activity. Here, we present evidence that Y. pseudotuberculosis selectively modulates Rho activity to induce cellular changes that control pore formation and effector translocation. Inhibition of actin polymerization decreased pore formation and YopE translocation in HeLa cells infected with Y. pseudotuberculosis. Inactivation of Rho, Rac, and Cdc42 by treatment with Clostridium difficile toxin B inhibited pore formation and YopE translocation in infected HeLa cells. Expression of a dominant negative form of Rac did not reduce the uptake of membrane impermeable dyes in HeLa cells infected with a pore forming strain YopEHJT−. Similarly, the Rac inhibitor NSC23766 did not decrease pore formation or translocation, although it efficiently hindered Rac-dependent bacterial uptake. In contrast, C. botulinum C3 potently reduced pore formation and translocation, implicating Rho A, B, and/or C in the control of the Yop delivery. An invasin mutant (Y. pseudotuberculosis invD911E) that binds to β1 integrins, but inefficiently transduces signals through the receptors, was defective for YopE translocation. Interfering with the β1 integrin signaling pathway, by inhibiting Src kinase activity, negatively affected YopE translocation. Additionally, Y. pseudotuberculosis infection activated Rho by a mechanism that was dependent on YopB and on high affinity bacteria interaction with β1 integrin receptors. We propose that Rho activation, mediated by signals triggered by the YopB/YopD translocon and from engagement of β1 integrin receptors, stimulates actin polymerization and activates the translocation process, and that once the Yops are translocated, the action of YopE or YopT terminate delivery of Yops and prevents pore formation

Los resultados adversos en el tratamiento de la tuberculosis resistente a múltiples fármacos sobrepasan la relación fármaco-microorganismo: resultados de un análisis de correspondencia múltiple

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.Introducción. El tratamiento de la tuberculosis multirresistente tiene una efectividad del 50 %, afectado por múltiples factores como la sensibilidad del microorganismo, las reacciones secundarias, los factores sociales y las comorbilidades existentes.Objetivos. Describir la demografía, las características clínicas y los factores pronósticos asociados con los resultados del tratamiento en pacientes multirresistentes (TB-MDR) de Medellín, Colombia.Métodos. Se hizo un análisis retrospectivo de los datos de los pacientes con TB-MDR atendidos en el Hospital La María de Medellín, Colombia, que fueron tratados entre el 2010 y el 2015. Los pacientes se categorizaron con tratamiento exitoso (curados) o con tratamiento fallido (falla en el tratamiento, pérdida durante el seguimiento y muerte). Se determinó la asociación entre las características demográficas y clínicas, los resultados de los exámenes de laboratorio, los desenlaces del tratamiento y la información del seguimiento, utilizando análisis univariado, multivariado y de correspondencia múltiple.Resultados. De 128 pacientes con TB-MDR, 77 (60 %) tuvieron un tratamiento exitoso. De los que tuvieron un tratamiento fallido, 26 pacientes se perdieron en el seguimiento, 15 murieron y 10 tuvieron falla en el tratamiento. El tratamiento irregular, las comorbilidades y los cultivos positivos más allá de 2 meses de tratamiento se asociaron significativamente con los tratamientos fallidos (p<0,05). El análisis de correspondencia múltiple agrupó los pacientes con pérdida en el seguimiento, con HIV y tratamientos irregulares, y los pacientes con tratamientos irregulares y enfermedad pulmonar obstructiva crónica con falla en el tratamiento y muerte.Conclusión. El reconocimiento temprano de los factores que afectan el desenlace del tratamiento de los pacientes con TB-MDR es esencial; la identificación de dichos factores debería incrementar el éxito del tratamiento y contribuir al adecuado control de la TB-MDR

IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

OBJECTIVES: Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNgamma produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNgamma levels in HHCs correlate with tuberculosis development. METHODS: A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. RESULTS: Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNgamma responders to CFP-10 (HR 1.82 95% CI 0.79-4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNgamma producers was observed (trend Log rank p = 0.007). DISCUSSION: CFP-10-induced IFNgamma production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprophylaxis to child contacts regardless of BCG vaccination

Relación del funcionamiento ejecutivo y procesos metacognitivos con el rendimiento académico en niños y niñas de primaria

El propósito del estudio fue analizar la relación entre el funcionamiento ejecutivo con el rendimiento académico en artes, ciencias, matemáticas y lenguaje. La muestra estuvo compuesta por 77 estudiantes de 6 a 9 años, sin diagnóstico clínico. Se aplicó el cuestionario de evaluación conductual del funcionamiento ejecutivo BRIEF para padres y madres. Los resultados mostraron que un mejor funcionamiento ejecutivo de los estudiantes en sus hogares, principalmente en procesos metacognitivos como la memoria de trabajo, la planificación, la iniciativa y el monitoreo, correlacionan con un rendimiento académico más alto tanto a nivel general como en cada área: artes, ciencias, matemáticas y lenguaje. Se concluye que el estudio del funcionamiento ejecutivo en contextos como el hogar y de su relación con diversas áreas académicas como artes y ciencias, además de matemáticas y lenguaje que han sido tradicionalmente observadas; contribuye a una comprensión más amplia e integradora de los factores que intervienen en el proceso de enseñanzaaprendizaje y en el funcionamiento cognitivo de los niños y las niñas.The purpose of the study was to analyze the relationship between the executive functioning and the academic performance in arts, science, mathematics and language. The sample consisted of 77 students aged from 6 to 9 years, without clinical diagnostics. The Behavior Rating Inventory of Executive Function BRIEF for parents was administered. The results showed that a better executive functioning of students in their homes, mainly in meta-cognitive processes such as working memory, planning, initiative and monitoring, correlate with the highest academic performance both in a general level and in each area: arts, sciences, mathematics and language. It is concluded that the study of executive functioning in contexts such as the home and its relationship with several academic areas such as arts and sciences, as well as mathematics and language that have traditionally been observed, contributes to a broader and more inclusive understanding of factors involved in the Teaching-learning process and the cognitive functioning of boys and girls

El psicoanálisis y la pasión: La posición del sujeto

El presente artículo es el resultado de una investigación de carácter conceptual, desde la perspectiva psicoanalítica, para mostrar cómo en la concepción de la enfermedad mental, Freud introduce la dimensión del sujeto en lo concerniente a la pulsión-pasión en la conformación de la neurosis. Freud, de formación médico-psiquiátrica, recibe de su tradición algunas concepciones etiológicas de la enfermedad en dos vías principales: La concepción de la enfermedad por vía de los accidentes externos e internos y por una concepción hereditaria o predisponente de la enfermedad, de la cual Freud toma distancia para pensar la enfermedad mental como realidad psíquica, introduciendo allí la responsabilidad del sujeto de su propio malestar, en tanto producto de conflictos que se generan en relación con la pulsión –pasión en el orden de lo sexual

La dimensión del Pathos en la Filosofía y en la Psiquiatria clásica

El presente artículo, es el resultado de una investigación de carácter conceptual, desde las perspectivas de la Filosofía y la Psiquiatría clásica, que hacen un recorrido por la enfermedad observando la variación que se tiene de la concepción del pathos, incluida en la línea de investigación: Subjetividad y Salud Mental, perteneciente al Grupo de Investigación en Psicología Sujeto, Sociedad y Trabajo, de la Universidad Pontificia Bolivariana, Medellín. El artículo tiene como objetivo rastrear el concepto del pathos en el mundo antiguo, en relación con la dimensión ética en tanto physis, en la Edad Media, donde se piensa a través de una concepción teológica del mundo, y en la Modernidad, donde el pathos se transforma en enfermedad mental a partir de la concepción científic

Funciones ejecutivas en niños y niñas de primaria : la importancia de las inteligencias múltiples como metodología de enseñanza-aprendizaje

Departament responsable de la tesi: Departament de Psicologia Bàsica, Evolutiva i de l'EducacióPremi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2016-2017El propósito de este trabajo ha sido investigar el funcionamiento ejecutivo (FE) en el contexto escolar. Durante el desarrollo de la investigación se realizaron dos estudios. El primero con el objetivo de contribuir al conocimiento sobre la relación entre la dimensión conductual del FE, en niños y niñas sin diagnóstico clínico; y el rendimiento académico en áreas que han sido menos observadas, como artes plásticas y ciencias naturales; además de matemáticas y lenguaje, que han sido tradicionalmente observadas. El segundo estudio se orientó por el interés en los factores del contexto escolar que pueden intervenir en el desarrollo del FE en la infancia; temática que ha sido menos abordada; sin embargo, existe literatura científica que indica que las características de las metodologías de enseñanza-aprendizaje pueden influir en el desarrollo del FE. En el primer estudio se empleó el cuestionario BRIEF para medir los aspectos comportamentales del FE, el cual fue contestado por los progenitores de los estudiantes; el rendimiento académico fue proporcionado por los maestros. Los resultados indicaron que el FE de los niños y niñas en sus hogares, principalmente en los componentes metacognitivos como memoria de trabajo, planificación, iniciativa y monitoreo, están significativamente asociados con un rendimiento académico más alto en todas las áreas académicas observadas. El segundo estudio se realizó con el objetivo de explorar, describir y analizar el FE en colegios con características metodológicas diferentes. Los colegios participantes eran equiparables en factores como el nivel socio-económico, y se diferenciaban en las características metodológicas. Uno de los colegios implementaba la perspectiva de las Inteligencias Múltiples (IM). Para este estudio, se emplearon además del cuestionario BRIEF, tres pruebas neuropsicológicas como medidas de desempeño cognitivo del FE de los estudiantes. Los resultados indicaron que los estudiantes del colegio IM presentaron mejores procesos ejecutivos de metacognición, regulación, iniciativa, monitoreo, planificación y control emocional, concretamente a nivel comportamental. También mejores procesos de flexibilidad tanto a nivel comportamental como cognitivo, así como mejor inhibición a nivel cognitivo; indicando que la implementación de metodologías basadas en la teoría de las IM, puede aportar al FE de los estudiantes. Las conclusiones de los estudios realizados en la presente investigación, aportan más evidencia de la importancia del FE en el proceso de enseñanza-aprendizaje y de que las características relacionadas con las metodologías de enseñanza-aprendizaje que se implementan en la escuela, son un factor que interviene en el FE de los estudiantes en primaria, principalmente de los procesos ejecutivos de regulación metacognitiva. El análisis de las implicaciones y aportes de la presente investigación integra elementos del contexto escolar, y señala que la implementación que una escuela hace de las metodologías pedagógicas, depende del enfoque educativo y del concepto de sujeto y sociedad, que estén prevaleciendo en el sistema educativo y social. Por lo tanto, la mejora tanto del aprendizaje como del FE no depende exclusivamente de las metodologías pedagógicas que se implementen. La teoría de las Inteligencias Múltiples presenta un enfoque particular sobre la educación y sobre el individuo y la sociedad, que implica el desarrollo de un FE en un nivel diferente al que se está considerando actualmente en el contexto escolar. Sus implicaciones metodológicas en la educación serían más aplicables en modelos educativos más centrados en el estudiante y el aprendizaje. De esta forma, esta reflexión convoca también a la observación, comprensión, y análisis crítico de los propósitos y finalidades actuales de la educación.The aim of this research has been to study the executive functioning (EF) in the scholar context. During the development of the research two studies were carried out. The first one aims to contribute to the knowledge about the relationship between the behavioral dimension of EF, in children without clinical diagnosis; and the academic achievement in areas that have been less observed, such as visual arts and natural sciences; in addition to mathematics and language, which have traditionally been observed. The second one was guided by the interest in the study of the factors of the school context that may intervene in the development of EF in childhood; which has been less addressed; however, there is scientific literature indicating that the characteristics of teaching-learning methodologies can influence the development of EF. In the first study, the BRIEF questionnaire was used to measure the behavioral aspects of EF, which was answered by the parents of the students; academic achievement was provided by teachers. The results indicated that the EF of children in their homes, mainly in the metacognitive components such as work memory, planning, initiative and monitoring, are significantly associated with a higher academic achievement in all the academic areas observed. The second study was carried out with the objective of exploring, describing and analyzing the EF in schools with different methodological characteristics. The participating schools were comparable in factors such as the socio-economic level, and differed in methodological characteristics. One of the schools implemented the Multiple Intelligences (MI) perspective. For this study, in addition to the BRIEF questionnaire, three neuropsychological tests were used as measures of students' cognitive performance of EF. The results indicated that students of MI school presented better executive processes of metacognition, regulation, initiative, monitoring, planning and emotional control, specifically at the behavioral level. They also presented better processes of flexibility at both the behavioral and cognitive level, as well as better inhibition at the cognitive level; which indicates that the implementation of methodologies based on the theory of MI, can contribute to the EF of the students. The conclusions of the studies carried out in the present work provide more evidence of the importance of EF in the teaching-learning process and also indicate the characteristics related to the methodologies implemented in the school are a factor that intervenes in the EF of students in primary, mainly in the executive processes of metacognitive regulation. The analysis of the implications and contributions of the present research integrates elements of the scholar context, and indicates that the implementation that a school makes of pedagogical methodologies depends on the educational approach and the concept of subject and society that prevailing in the educational and social system. Therefore, the improvement of both learning and EF does not depend exclusively on the pedagogical methodologies that are implemented. The theory of Multiple Intelligences presents a particular perspective on education and on the individual and society, which implies the development of an EF at a level different from what is currently being considered in the school context. The methodological implications of the MI theory in education would be more applicable in educational models more centered on the student. In this way, this reflection also calls for the observation, understanding, and critical analysis of the current finality and purposes of education

Factores de riesgo para el desarrollo de Tuberculosis multidrogorresistente en Colombia, 2008 A 2011

Objective Determining the risk factors associated with developing multidrug-resistant tuberculosis in people aged over 18 years affiliated to 3 Colombian health insurance companies between 2008 and 2011. Methods The study involved a matched case-control design (1 case to 4 controls). Patients were identified from 3 health insurance companies’ tuberculosis program database; this gave 45 cases and 180 controls. Demographic, socioeconomic and clinical variables were evaluated. Results The median age for cases was 43 years (39.5 years for controls); males predominated in cases (73.3 %) while women predominated in controls (51.1 %). A statistically significant association was found between multidrug-resistant tuberculosis and being male (4.47 adjusted OR; 1.01-19.75 95 %CI), having subsidized social security cover (57.6 adjusted OR; 4.6-71.28 95 %CI) and having had prior treatment for tuberculosis (56.2 adjusted OR; 10.03-314.79 95 % CI]. Conclusions Prior treatment for tuberculosis and being male were risk factors for developing multidrug resistance. Further studies are needed with the Colombian health system to clarify the findings with respect to being affiliated to a subsidized health system and the development of multidrug resistant tuberculosis. © 2016, Universidad Nacional de Colombia. All rights reserved

Single Nucleotide Polymorphism in the IL17A Gene Is Associated with Interstitial Lung Disease Positive to Anti-Jo1 Antisynthetase Autoantibodies

Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we divided the case group into anti-Jo1 and non-anti-Jo1. Two single nucleotide polymorphisms (SNPs) in the IL17A gene were evaluated. Anti-Jo1 was the most common anti-tRNA antibody in our cohort, and the most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP). Anti-Jo1 ASSD patients had higher levels of creatine phosphokinase than the non-anti-Jo1 group. Significant differences in genotype frequencies with rs8193036/CC between anti-Jo1 vs. non-anti-Jo1 ASSD patients (p &lt; 0.001), maintaining the association after Bonferroni correction (p = 0.002). Additionally, in the anti-Jo1 group vs. HS comparison, we found a statistically significant difference with the same SNP (p = 0.018, OR = 2.91, 95% CI = 1.15–7.35), maintaining the association after Bonferroni correction (p = 0.036). The rs8193036/CC genotype in IL17A is associated with ASSD patients with anti-Jo1. Also, anti-Jo1 and non-anti-Jo1 patients display differences in genotype frequencies

Ultra-processed food consumption and breast cancer risk

Objectives: The consumption of ultra-processed foods (UPF) has been linked to an increased risk of cancer in western populations, particularly for breast cancer (BC). Although the consumption of UPF is increasing rapidly in Latin American (LA) populations too, there has been no evaluation of its association with BC among LA women, where 20% of the BC cases present at ages younger than 45 years. We therefore evaluated the role of UPF intake on BC risk in young women participating in the Latin American PRECAMA study. Methods: The PRECAMA study is an ongoing study coordinated by the International Agency for Research on Cancer (IARC) and involves scientific teams in four LA countries (Chile, Colombia, Costa Rica and Mexico); 406 incident BC cases and population based controls aged 20–45 years are recruited. Trained nurses administered a lifestyle and food frequency questionnaires (FFQ), conducted anthropometric measurements and collected biological samples. Tumour receptor status are determined in a centralized laboratory. UPF consumption was estimated by applying the NOVA classification to the dietary consumption data obtained via the FFQs. The association of the consumption of UPF and BC was determined using conditional logistic regression analysis adjusting for potential confounding factors. Results: The median age at recruitment was 40 years. The median percentage of calories from UPF was 24% (10th to 90th percentile: 9 to 43%). UPF intake was positively associated with BC risk (OR for tertiles 2 and 3 in comparison with tertile 1 were 1.84 (95% CI 1.21 -2.81) and 1.69 (95% CI 0.99 -2.89) respectively). Among the UPF most strongly associated with BC, we identified the intake of industrial bread, packaged sweet and savoury snacks, breakfast cereals, cakes and desserts, and ready-eat/fast food. Comparing the 3rd with the 1st tertile of energy intake from the UPF group “fast food” the OR for BC risk was 1.93 (95% CI 1.23–3.04). Discussion: Our results show positive associations between the consumption of UPF and BC risk in young women in LA. Therefore, global actions to decrease UPF intakes are urgently needed to address the cancer burden. In addition, further studies are needed to disentangle mechanisms relating UPF intake and carcinogenic processes in the breast. The European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large-scale cohort including ∼500,000 participants and 18,814 BC cases will be used to unravel the mechanistic pathways underlying these positive associations between the consumption of UPF and BC risk