Síndrome del incisivo central maxilar único: reporte de caso

El síndrome del incisivo central maxilar único es una rara alteración en el desarrollo y formación de órganos ubicados principalmente en la línea media; el cual ocurre de manera temprana entre los días 35 al 38 de vida intrauterina. Su etiología es desconocida, aunque se ha asociado a deleciones de los cromosomas 7 (7q.36.1) y 8, y a mutaciones en el gen Sonic Hedgehog. Presenta una prevalencia de 1/50.000 nacidos vivos y aunque es una anomalía poco frecuente del desarrollo craneofacial, su diagnóstico y tratamiento temprano son importantes para los odontólogos generales o especialistas ya que puede ser un signo de otras anomalías congénitas o del desarrollo graves. Por lo tanto, el objetivo de este caso es reportar la fase inicial de tratamiento en un niño con el síndrome de incisivo central maxilar único quien no había sido diagnosticado anteriormente con este síndrome. Caso Clínico: Paciente masculino de 10 años de edad, procedente de Jamundí, Valle del Cauca- Colombia. Reporta ausencia de órgano dentario superior. En el examen intraoral se observa un incisivo central único sobre la línea media del maxilar, ausencia de frenillo labial y papila incisiva, paladar oval y retrognatismo mandibular. Fue tratado en una primera fase con ortopedia funcional maxilar para mejorar la clase II y está a la espera de iniciar la segunda fase de tratamiento con ortodoncia. Conclusiones: El síndrome de incisivo central maxilar único es un síndrome poco frecuente el cual conlleva múltiples afecciones que interfieren en el normal desarrollo y crecimiento de estructuras anatómicas.

A síndrome do incisivo central superior único é uma alteração rara no desenvolvimento e formação de órgãos localizados principalmente na linha média; que ocorre precocemente entre os dias 35 a 38 de vida intrauterina. Sua etiologia é desconhecida, embora tenha sido associada a deleções dos cromossomos 7 (7q.36.1) e 8, e mutações no gene Sonic Hedgehog. Tem uma prevalência de 1/50.000 nascidos vivos e, embora seja uma anomalia rara do desenvolvimento craniofacial, seu diagnóstico e tratamento precoces são importantes para dentistas gerais ou especialistas, pois pode ser sinal de outras anomalias congênitas ou de desenvolvimento graves. Portanto, o objetivo deste caso é relatar a fase inicial do tratamento em uma criança com síndrome do incisivo central superior único que não havia sido previamente diagnosticada com essa síndrome. Caso clínico: Paciente do sexo masculino, 10 anos, procedente de Jamundí, Valle del Cauca- Colômbia. Relata ausência de órgão dentário superior. O exame intraoral mostra um único incisivo central na linha média maxilar, ausência de frênulo labial e papila incisiva, palato oval e retrognatismo mandibular. Foi tratado numa primeira fase com ortopedia funcional maxilar para melhorar a classe II e aguarda para iniciar a segunda fase do tratamento ortodôntico. Conclusões: A síndrome do incisivo central superior único é uma síndrome rara que envolve múltiplas condições que interferem no desenvolvimento e crescimento normal das estruturas anatômicas.

Solitary maxillary central incisor syndrome is a rare alteration in the development and formation of organs located mainly in the midline; which occurs early between days 35 to 38 of intrauterine life. Its etiology is unknown, although it has been associated with deletions of chromosomes 7 (7q.36.1) and 8, and mutations in the Sonic Hedgehog gene. It has a prevalence of 1/50,000 live births and although it is a rare anomaly of craniofacial development, its early diagnosis and treatment are important for general dentists or specialists since it can be a sign of other serious congenital or developmental anomalies. Therefore, the objective of this case is to report the initial phase of treatment in a child with solitary maxillary central incisor syndrome who had not been previously diagnosed with this syndrome. Clinical case: Male patient, 10 years old, from Jamundí, Valle del Cauca- Colombia. Reports absence of upper dental organ. Intraoral examination shows a solitary central incisor on the maxillary midline, absence of labial frenulum and incisive papilla, oval palate and mandibular retrognathism. He was treated in a first phase with maxillary functional orthopedics to improve class II and is waiting to start the second phase of orthodontic treatment. Conclusions: Solitary maxillary central incisor syndrome is a rare syndrome which involves multiple conditions that interfere with the normal development and growth of anatomical structures.

Parto Prematuro: Tratamiento con nifedipino versus atosiban. Revisión Bibliográfica Teórica / Preterm Labor: nifedipine vs atosiban treatment. Bilbiographic theoretical review

Introducción: La amenaza de parto pretérmino es un problema de salud pública mundial y nacional. La prematuridad viene acompañada de complicaciones como inmadurez pulmonar y lesiones del sistema nervioso central, que requieren de tratamiento oportuno.Objetivo: Establecer una comparación objetiva de los resultados del tratamiento de la ame-naza de parto prematuro, mediante el uso de Nifedipina o Atosiban, realizando una revisión teórica actualizada del tema, con el propósito de ofrecer a la comunidad científica, una he-rramienta de consulta, sobre un tema frecuente y de alto riesgo materno fetal.Materiales y Métodos: Se realizó una búsqueda bibliográfica en las bases de datos: Google Scholar, Pubmed, Wiley Online Library, Biomed, Scopus, Medes, Medline, Pro Quest, Gale, Scopus, y ScIELO, Se incluyeron artículos publicados en revistas indexadas de alto impacto, en los últimos 5 años. Se valoró la calidad de los artículos incluidos, utilizando la metodología de Sacket, y el riesgo de sesgo, según la metodología Cochrane. Resultados: Se observó un consenso entre los autores consultados en que no existen dife-rencias significativas en el efecto tocolítico de atosiban y nifedipino Conclusiones:La literatura académica parece coincidir en que la efectividad de atosiban y ni-fedipino como agentes tocolíticos es similar, con ambos medicamentos se consigue prolongar el embarazo con riesgo de parto pretérmino, que es el propósito fundamental de la tocolisis.

Background: The threat of preterm birth is a global and national public health problem. Prematurity is linked to complications such as pulmonary immaturity and central nervous system lesions, which require timely treatment. Objective: To perform an objective comparison of the results of the treatment of the threat of premature delivery, using nifedipine or atosiban, carrying out an updated theoretical review of the subject, to offer the scientific community a tool for research on a frequent subject of high maternal and fetal risk. Materials y Methods: There was a bibliographic search in specialized databases. Articles published in high impact indexed journals in the last 5 years were included. The quality of the articles included was assessed, using the Sacket methodology, and the risk of bias, accor-ding to the Cochrane methodology. Results: There was an agreement among the authors consulted there are no significant differences in the tocolytic effect of atosiban and nifedipine. Conclusions: The academic literature seems to agree that the effectiveness of atosiban and nifedipine as tocolytic agents is similar, with both drugs prolonging pregnancy with the risk of preterm delivery, which is the fundamental purpose of tocolysis.

Revisión sobre los estudios en el campo académico de la discapacidad y las personas con discapacidad / Review on Studies in the Academic Field of Disability and Persons with Disabilities

Resumen El propósito de este trabajo es presentar un estado del arte sobre los estudios en el campo académico de la discapacidad en un intento por aportar elementos teóricos a quienes vienen trabajando la discapacidad como problema social y no como un asunto de tipo médico y rehabilitador. Se realizó una revisión documental de artículos de investigación, capítulos de libros y libros en diversas bases de datos donde se analizaron 55 fuentes documentales utilizando como técnica el análisis documental a partir del instrumento de la regilla documental. Entre los resultados se destaca que los problemas sobre los que ha girado el estudio de la discapacidad han sido en educación inclusiva, desarrollo humano, justicia social, estudios decoloniales y críticos de la discapacidad, y alrededor de la identidad y el reconocimiento. Se concluye que aún prevalece una mirada a la discapacidad y las personas con discapacidad desde la deficiencia, la superación, la rehabilitación y la limitación, y aunque existen estudios que interpelan a los sujetos con discapacidad, en estos prevalecen los abordajes alrededor de los obstáculos o elementos facilitadores para la inclusión.

Abstract This paper aims to present the state of art on research in the academic field of disability in an attempt to provide theoretical elements to those who have been working on disability as a social problem and not as a medical and rehabilitative issue. A documentary review of research articles, book chapters, and books in various databases was carried out. Fifty-five documentary sources were analyzed using the documentary analysis technique based on the documentary grid instrument. Among the results, it is highlighted that the study of disability has revolved around the aspects of inclusive education, human development, social justice, decolonial and critical studies of disability, and identity and recognition. It is concluded that disability and persons with disabilities are still viewed from the point of view of impairment, overcoming, rehabilitation, and limitation, and although there are studies that question subjects with disabilities, these studies focus on the obstacles or facilitating elements for inclusion.

Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis.

The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.

Paracoccidioides spp. catalases and their role in antioxidant defense against host defense responses.

Dimorphic human pathogenic fungi interact with host effector cells resisting their microbicidal mechanisms. Yeast cells are able of surviving within the tough environment of the phagolysosome by expressing an antioxidant defense system that provides protection against host-derived reactive oxygen species (ROS). This includes the production of catalases (CATs). Here we identified and analyzed the role of CAT isoforms in Paracoccidioides, the etiological agent of paracoccidioidomycosis. Firstly, we found that one of these isoforms was absent in the closely related dimorphic pathogen Coccidioides and dermatophytes, but all of them were conserved in Paracoccidioides, Histoplasma and Blastomyces species. We probed the contribution of CATs in Paracoccidioides by determining the gene expression levels of each isoform through quantitative RT-qPCR, in both the yeast and mycelia phases, and during the morphological switch (transition and germination), as well as in response to oxidative agents and during interaction with neutrophils. PbCATP was preferentially expressed in the pathogenic yeast phase, and was associated to the response against exogenous H2O2. Therefore, we created and analyzed the virulence defects of a knockdown strain for this isoform, and found that CATP protects yeast cells from H2O2 generated in vitro and is relevant during lung infection. On the other hand, CATA and CATB seem to contribute to ROS homeostasis in Paracoccidioides cells, during endogenous oxidative stress. CAT isoforms in Paracoccidioides might be coordinately regulated during development and dimorphism, and differentially expressed in response to different stresses to control ROS homeostasis during the infectious process, contributing to the virulence of Paracoccidioides.

A Colombian diabetes risk score for detecting undiagnosed diabetes and impaired glucose regulation.

AIMS: (i) To develop a diabetes mellitus risk score model for the Colombian population (ColDRISC); and (ii) to evaluate the accuracy of the ColDRISC unknown Type 2 diabetes mellitus METHODS: Cross-sectional screening study of the 18-74 years-old population of a health-care insurance company (n=2060) in northern Colombia. Lifestyle habits and risk factors for diabetes mellitus were assessed by an interview using a questionnaire consisting of information regarding sociodemographic factors, history of diabetes mellitus, tobacco consumption, hypertension, nutritional and physical activity habits. Anthropometric measurements and an oral glucose tolerance test were taken. The sensitivity and the specificity, receiver-operating characteristic (ROC) curves, were calculated for the ColDRISC and FINDRISC. RESULTS: The area under the ROC curve for unknown Type 2 diabetes mellitus was 0.74 (95% CI: 0.70-0.79) for the ColDRISC and 0.73 for the FINDRISC (95% confidence intervals [CI] 0.69-0.78). Using the risk score cutoff value of 4 in the ColDRISC to detect Type 2 diabetes mellitus resulted in a sensitivity of 73% and specificity of 67%. CONCLUSIONS: The characteristics of the ColDRISC show that it can be used as a simple, safe, and inexpensive test to identify people at high risk for Type 2 diabetes mellitus in Colombia.

Identification and Analysis of the Role of Superoxide Dismutases Isoforms in the Pathogenesis of Paracoccidioides spp.

The ability of Paracoccidioides to defend itself against reactive oxygen species (ROS) produced by host effector cells is a prerequisite to survive. To counteract these radicals, Paracoccidioides expresses, among different antioxidant enzymes, superoxide dismutases (SODs). In this study, we identified six SODs isoforms encoded by the Paracoccidioides genome. We determined gene expression levels of representative isolates of the phylogenetic lineages of Paracoccidioides spp. (S1, PS2, PS3 and Pb01-like) using quantitative RT-PCR. Assays were carried out to analyze SOD gene expression of yeast cells, mycelia cells, the mycelia-to-yeast transition and the yeast-to-mycelia germination, as well as under treatment with oxidative agents and during interaction with phagocytic cells. We observed an increased expression of PbSOD1 and PbSOD3 during the transition process, exposure to oxidative agents and interaction with phagocytic cells, suggesting that these proteins could assist in combating the superoxide radicals generated during the host-pathogen interaction. Using PbSOD1 and PbSOD3 knockdown strains we showed these genes are involved in the response of the fungus against host effector cells, particularly the oxidative stress response, and in a mouse model of infection. Protein sequence analysis together with functional analysis of knockdown strains seem to suggest that PbSOD3 expression is linked with a pronounced extracellular activity while PbSOD1 seems more related to intracellular requirements of the fungus. Altogether, our data suggests that P. brasiliensis actively responds to the radicals generated endogenously during metabolism and counteracts the oxidative burst of immune cells by inducing the expression of SOD isoforms.

Paracoccidioides brasiliensis PbP27 gene: knockdown procedures and functional characterization.

Paracoccidioides brasiliensis PbP27 gene encodes a protein localized in both the fungal cytoplasm and cell wall. The parasitic infectious form produces this protein preferentially with the gene's expression varying between the fungus phylogenetic species. The biological function of the native p27 has yet to be determined during either growth of the yeast or host infection. Therefore, in this study, through the use of antisense RNA technology and Agrobacterium tumefaciens-mediated transformation, we generated mitotically stable PbP27 mutants (PbP27 aRNA) with the goal to evaluate the role of p27 in the biology and virulence of this fungus. PbP27 expression was reduced 60-75% in mutants, as determined by real-time PCR in correlation with a decrease in p27 expression. No alterations in the growth curve or in the ability to shift from mycelia to yeast or from yeast to mycelia were observed in PbP27 aRNA strains; however, we did observe a reduction in cell vitality. Moreover, a decrease in cell viability of PbP27 aRNA yeast cells after interaction with IFN-γ-stimulated macrophages was detected. Based on these results, we propose that p27 plays a role in yeast cell architecture and represents one of the mechanisms employed by this fungus for its interaction with the monocyte/macrophage system.

Costos ambulatorios y hospitalarios de la falla cardiaca en dos hospitales de Bogotá / Outpatient and inpatient costs of heart failure in two hospitals in Bogotá

Objetivo: realizar una aproximación a la determinación de costos directos de la falla cardiaca (FC) en el país, a través de la evaluación de costos asociados con el cuidado de pacientes atendidos en dos instituciones prestadoras de salud de Bogotá. Métodos: estudio de costos bajo la perspectiva del tercer pagador. La identificación de eventos generadores de costos en atención ambulatoria se realizó mediante revisión de historias clínicas de pacientes atendidos durante 2011 en la consulta externa especializada de una institución. Los costos de interconsultas y paraclínicos se determinaron según los valores del Acuerdo 256 de 2001, con adición de 30%. Los costos de la medicación se determinaron a partir del registro SISMED. La identificación de eventos generadores de costos en hospitalización se realizó mediante revisión de listados y facturas de pacientes atendidos entre 2009 y 2010 en dos instituciones. Los resultados se presentan resumidos por medidas de tendencia central y de dispersión, en pesos colombianos (COP) de 2011. Resultados: el costo mensual promedio del tratamiento ambulatorio de FC fue de 304.318 COP (D.E. 760.876), con una mediana de 45.280 COP (RIC 25.539 - 109.715); los medicamentos representaron la fuente principal de consumo de recursos (55,2%). El costo promedio de la hospitalización por descompensación de FC fue de 6.427.887 COP (D.E. 9.663.176); la estancia hospitalaria representó la mayor proporción del costo (29,1%). Conclusiones: los costos ambulatorios, y especialmente los hospitalarios, asociados con la FC en Colombia son sustanciales. La fuente principal de costos difiere dependiendo de si el manejo es hospitalario (estancia) o ambulatorio (medicamentos). (Acta Med Colomb 2013; 38: 208-212).

Objective: to make an approach to the determination of direct costs of heart failure (HF) in the country through the evaluation of costs associated with the care of patients seen in two health institutions in Bogota. Methods: low cost third-party payer perspective. Identification of cost generating events in ambulatory care was performed by review of medical records of patients seen during 2011 in the specialized outpatient clinic of an institution. Interconsultations and paraclinical costs were determined according to the 256 Agreement of 2001, with addition of 30%. Medication costs were determined from the SISMED register. Identification of events that generate costs in hospitalization was conducted by reviewing lists and bills of patients treated between 2009 and 2010 in two institutions. The results are presented summarized by measures of central tendency and dispersion, in Colombian pesos (COP) of 2011. Results: the average monthly cost for outpatient treatment of HF was 304,318 COP (D.E. 760 876), with a median of 45,280 COP (RIC 25,539-109,715); drugs represented the main source of resource consumption (55.2%). The average cost of hospitalization for decompensated HF was 6,427,887 COP (D.E. 9.663.176); hospital stay accounted for the largest proportion of the cost (29.1%). Conclusions: outpatient costs, and especially the inpatient ones associated with HF in Colombia are substantial. The main source of costs differs depending on whether the management is hospitable (stay) or outpatient (drugs). (Acta Med Colomb 2013; 38: 208-212).

Inhibition of PbGP43 expression may suggest that gp43 is a virulence factor in Paracoccidioides brasiliensis.

Glycoprotein gp43 is an immunodominant diagnostic antigen for paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly secreted in isolates such as Pb339. It is structurally related to beta-1,3-exoglucanases, however inactive. Its function in fungal biology is unknown, but it elicits humoral, innate and protective cellular immune responses; it binds to extracellular matrix-associated proteins. In this study we applied an antisense RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type Pb339 to study its role in P. brasiliensis biology and during infection. Control PbEV was transformed with empty vector. Growth curve, cell vitality and morphology of PbGP43 aRNA mutants were indistinguishable from those of controls. PbGP43 expression was reduced 80-85% in mutants 1 and 2, as determined by real time PCR, correlating with a massive decrease in gp43 expression. This was shown by immunoblotting of culture supernatants revealed with anti-gp43 mouse monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays of extracellular molecules with laminin and fibronectin. In vitro, there was significantly increased TNF-α production and reduced yeast recovery when PbGP43 aRNA1 was exposed to IFN-γ-stimulated macrophages, suggesting reduced binding/uptake and/or increased killing. In vivo, fungal burden in lungs of BALB/c mice infected with silenced mutant was negligible and associated with decreased lung ΙΛ-10 and IL-6. Therefore, our results correlated low gp43 expression with lower pathogenicity in mice, but that will be definitely proven when PbGP43 knockouts become available. This is the first study of gp43 using genetically modified P. brasiliensis.

Interaction between Paracoccidioides brasiliensis conidia and the coagulation system: involvement of fibrinogen

The infectious process starts with an initial contact between pathogen and host. We have previously demonstrated that Paracoccidioides brasiliensis conidia interact with plasma proteins including fibrinogen, which is considered the major component of the coagulation system. In this study, we evaluated the in vitro capacity of P. brasiliensis conidia to aggregate with plasma proteins and compounds involved in the coagulation system. We assessed the aggregation of P. brasiliensis conidia after incubation with human serum or plasma in the presence or absence of anticoagulants, extracellular matrix (ECM) proteins, metabolic and protein inhibitors, monosaccharides and other compounds. Additionally, prothrombin and partial thromboplastin times were determined after the interaction of P. brasiliensis conidia with human plasma. ECM proteins, monosaccharides and human plasma significantly induced P. brasiliensis conidial aggregation; however, anticoagulants and metabolic and protein inhibitors diminished the aggregation process. The extrinsic coagulation pathway was not affected by the interaction between P. brasiliensis conidia and plasma proteins, while the intrinsic pathway was markedly altered. These results indicate that P. brasiliensis conidia interact with proteins involved in the coagulation system. This interaction may play an important role in the initial inflammatory response, as well as fungal disease progression caused by P. brasiliensis dissemination.

Involvement of the 90 kDa heat shock protein during adaptation of Paracoccidioides brasiliensis to different environmental conditions.

HSP90 is a molecular chaperone that participates in folding, stabilization, activation, and assembly of several proteins, all of which are key regulators in cell signaling. In dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, the adaptation to a higher temperature, acid pH and oxidative stress, is an essential event for fungal survival and also for the establishing of the infectious process. To further understand the role of this protein, we used antisense RNA technology to generate a P. brasiliensis isolate with reduced PbHSP90 gene expression (PbHSP90-aRNA). Reduced expression of HSP90 decreased yeast cell viability during batch culture growth and increased susceptibility to acid pH environments and imposed oxidative stress. Also, PbHSP90-aRNA yeast cells presented reduced viability upon interaction with macrophages. The findings presented here suggest a protective role for HSP90 during adaptation to hostile environments, one that promotes survival of the fungus during host-pathogen interactions.

The hydrolase PbHAD32 participates in the adherence of Paracoccidioides brasiliensis conidia to epithelial lung cells.

Adherence of the dimorphic pathogenic fungus Paracoccidioides brasiliensis to lung epithelial cells is considered an essential event for the establishment of infection. We have previously shown that the PbHAD32 hydrolase is important in this early stage of the host-P. brasiliensis yeast cells interaction. The aim of this study was to further elucidate the role of PbHAD32 in conidial thermodimorphism and their interaction with lung epithelial cells. Analysis of the PbHAD32 gene expression revealed higher mRNA levels during the conidia to mycelia (C-M) germination when compared to the conidia to yeast (C-Y) transition. Moreover, PbHAD32 was consistently expressed at higher levels upon infection of lung epithelial cells, but to a greater extent when conidia germinated to produce mycelia. Interestingly, at this particular transitional stage, more conidia adhered to epithelial cells than when they were transiting to the yeast form. Altogether our data further corroborates the importance of PbHAD32 during initial adherence to host cells and suggest that the 32-KDa hydrolase may also participate at different stages of the C-M and C-Y conversions.

Kinetic analysis of gene expression during mycelium to yeast transition and yeast to mycelium germination in Paracoccidioides brasiliensis / Análisis de la cinética de expresión de genes durante la transición de micelio a levadura y la germinación levadura a micelio en Paracoccidioides brasiliensis

Introduction: Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus that in tissues and cultures at 37°C grows as a yeast while at lower temperatures (less than 24°C) it becomes a mold; however the genes that rule these processes and their expression are poorly understood. Objective: This research focused on the kinetic expression of certain genes in P. brasiliensis throughout the dimorphic process, one that involves the transition from the mycelium to yeast forms and the germination from the yeast to mycelium form. Materials and methods: A real-time quantitative polymerase chain reaction (RT-qPCR) was optimized to measure the expression of ten genes connected with diverse cellular functions including cell synthesis and wall structure, oxidative stress response, heat shock response, metabolism, proteins’ processing, solute transport across the cell membrane and signal transduction pathways at different time points during the mycelia to yeast transition, as well as in the yeast to mycelia germination processes. Results: Genes involved in cell synthesis and wall structure, metabolism and signal transduction were differentially expressed and highly up-regulated during the yeast to mycelia germination process; on the other hand, genes involved in heat shock response, cell synthesis and wall structure were highly up-regulated during the mycelia to yeast transition process. The remaining genes were differentially regulated during both processes. Conclusion: In this work the up-regulation of certain genes involved in the morphological changes occurring in P. brasiliensis yeast and mycelia forms were confirmed, indicating that these biological processes play an important role during the host-pathogen interactions, as well as in the fungus adaptation to environmental conditions.

Introducción. La paracoccidioidomicosis es una micosis sistémica causada por el hongo termodimorfo Paracoccidioides brasiliensis. En tejidos y cultivos a 37°C crece como levadura, mientras que a temperaturas menores de 24°C crece como un moho. Sin embargo, se conoce poco sobre los genes que regulan estos procesos. Objetivo. Se evaluó la cinética de expresión de algunos genes en P. brasiliensis mediante el proceso de dimorfismo incluida la transición del micelio a levadura y de la germinación de levadura a micelio. Materiales y métodos. Se optimizó una PCR cuantitativa en tiempo real (RT-qPCR) para medir la expresión de diez genes relacionados con diversas funciones celulares que incluyeron: síntesis de pared, respuesta al estrés oxidativo, respuesta al choque térmico, metabolismo, procesamiento de proteínas, trasporte de solutos a través de membranas y transducción de señales, todo ello a diferentes tiempos durante la transición de micelio a levadura, así como de la germinación de levadura a micelio. Resultados. Se encontró que los genes relacionados con síntesis de pared, metabolismo y transducción de señales, se expresaban de manera diferencial y con regulación positiva durante la germinaciónlevadura a micelio, mientras que algunos genes relacionados con respuesta a choque térmico y a síntesis de pared estaban sobreexpresados en la transición de micelio a levadura. Los genes restantes se regularon de manera diferencial en ambos procesos. Conclusiones. En este trabajo se confirma la regulación positiva de algunos genes relacionados con los cambios morfológicos de las fases levadura y micelio en P. brasiliensis, procesos biológicos que juegan un papel de importancia durante la interacción huésped-parásito y durante la adaptación del hongo al ambiente, respectivamente.

Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection.

BACKGROUND: Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells. AIMS AND METHODOLOGY: In this study, we evaluated the role of alternative oxidase (AOX), an enzyme involved in the intracellular redox balancing, during host-P. brasiliensis interaction. We generated a mitotically stable P. brasiliensis AOX (PbAOX) antisense RNA (aRNA) strain with a 70% reduction in gene expression. We evaluated the relevance of PbAOX during interaction of conidia and yeast cells with IFN-γ activated alveolar macrophages and in a mouse model of infection. Additionally, we determined the fungal cell's viability and PbAOX in the presence of H2O2. RESULTS: Interaction with IFN-γ activated alveolar macrophages induced higher levels of PbAOX gene expression in PbWt conidia than PbWt yeast cells. PbAOX-aRNA conidia and yeast cells had decreased viability after interaction with macrophages. Moreover, in a mouse model of infection, we showed that absence of wild-type levels of PbAOX in P. brasiliensis results in a reduced fungal burden in lungs at weeks 8 and 24 post-challenge and an increased survival rate. In the presence of H2O2, we observed that PbWt yeast cells increased PbAOX expression and presented a higher viability in comparison with PbAOX-aRNA yeast cells. CONCLUSIONS: These data further support the hypothesis that PbAOX is important in the fungal defense against oxidative stress imposed by immune cells and is relevant in the virulence of P. brasiliensis.

A 32-kilodalton hydrolase plays an important role in Paracoccidioides brasiliensis adherence to host cells and influences pathogenicity.

One of the most crucial events during infection with the dimorphic fungus Paracoccidioides brasiliensis is adhesion to pulmonary epithelial cells, a pivotal step in the establishment of disease. In this study, we have evaluated the relevance of a 32-kDa protein, a putative adhesion member of the haloacid dehalogenase (HAD) superfamily of hydrolases, in the virulence of this fungus. Protein sequence analyses have supported the inclusion of PbHad32p as a hydrolase and have revealed a conserved protein only among fungal dimorphic and filamentous pathogens that are closely phylogenetically related. To evaluate its role during the host-pathogen interaction, we have generated mitotically stable P. brasiliensis HAD32 (PbHAD32) antisense RNA (aRNA) strains with consistently reduced gene expression. Knockdown of PbHAD32 did not alter cell vitality or viability but induced morphological alterations in yeast cells. Moreover, yeast cells with reduced PbHAD32 expression were significantly affected in their capacity to adhere to human epithelial cells and presented decreased virulence in a mouse model of infection. These data support the hypothesis that PbHad32p binds to extracellular matrix (ECM) proteins and modulates the initial immune response for evasion of host defenses. Our findings point to PbHAD32 as a novel virulence factor active during the initial interaction with host cells in P. brasiliensis.

Mujeres en tratamiento de cáncer, acogidas por un albergue de apoyo: circunstancias y perspectivas de cuidado de enfermería / Women receiving cancer treatment supported by a housing support: circumstances and perspectives in nursing care

Se realizó un estudio de tipo cualitativo basado en 13 entrevistas a profundidad a mujeres con cáncer entre los 33 y los 70 años, con diferentes diagnósticos, provenientes de varias regiones de Colombia, vinculadas al régimen subsidiado, y que son acogidas por un albergue durante su estadía en Bogotá con motivo de su tratamiento en el Instituto Nacional de Cancerología (INC) con el fin de conocer sus circunstancias y sus necesidades de cuidado de enfermería. De las mujeres, 8 tienen un cáncer de tipo ginecológico y de este grupo 5 viven con cáncer de mama. En 4 de los 13 casos el diagnóstico fue tardío. Para todas las mujeres ha sido difícil asimilar su diagnóstico, asociándolo a la posibilidad de morir; luego ha sobrevenido una etapa de aceptación de su realidad de salud y de afrontamiento. Para este grupo, el INC y el Albergue constituyen redes sociales significativas; la lejanía de sus allegados es una dificultad que destacan del hecho de tener que desplazarse a la capital. La mayoría de las participantes buscan sentirse activas; los aspectos psicosociales son prioritarios entre sus necesidades; desean profundizar en su conocimiento de la enfermedad; es importante para ellas desarrollar mayores habilidades de auto cuidado para minimizar efectos adversos y síntomas. Fortalecer las redes de acompañamiento e interacción generadas entre ellas así como apoyarlas para fortalecer sus perspectivas de afrontamiento de su enfermedad y de autocuidado hacen parte de las estrategias que se proponen para otorgar mayor sentido a la cotidianidad y para favorecer su salud mental y su calidad de vida durante el tiempo que duran sus tratamientos en la capital.