Orphan nuclear receptor COUP-TFII enhances myofibroblast glycolysis leading to kidney fibrosis.

Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts also induced production of alpha-smooth muscle actin (αSMA) and collagen 1. Knockout of COUP-TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.

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.

Alternative oxidase plays an important role in Paracoccidioides brasiliensis cellular homeostasis and morphological transition.

Paracoccidioides brasiliensis is the etiologic agent of one of the most common systemic mycoses in Latin America. As a dimorphic fungus, it must adapt to different environments during its life cycle, either in nature or within the host, enduring external stresses such as temperature or host-induced oxidative stress. In this study we addressed the role of alternative oxidase (PbAOX) in cellular homeostasis during batch culture growth and the morphological transition of P. brasiliensis. Using a PbAOX-antisense-RNA (PbAOX-aRNA) strain with a 70% reduction in gene expression, we show that PbAOX is crucial for maintaining cell viability and vitality during batch culture growth of yeast cells, in what appears to be a pH-dependent manner. We also show that silencing of PbAOX drastically reduced expression levels of other detoxifying enzymes (PbY20 and PbMSOD). In addition, our data indicate that PbAOX plays a role during the morphological transition, namely, during the yeast-to-mycelia germination and mycelia/conidia-to-yeast transition, essential events during the establishment of infection by dimorphic fungal pathogens. Altogether, our findings support the hypothesis that PbAOX is important for the maintenance of cellular homeostasis, possibly by assisting redox balancing during cell growth and the morphological switch of P. brasiliensis.

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.

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.

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.

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.

Are you ready for retirement? The influence of values on membership in voluntary organizations in midlife and old age.

Membership in voluntary organizations is associated with individual and social benefits. Due to the negative consequences of the global pandemic on older people, and the governmental challenges posed by population aging, voluntary membership is of great importance to society. To effectively promote volunteering among older people, it is necessary to understand the determinants of voluntary membership. This study analyses the influence of individual values-secular/traditional and survival/self-expression-on voluntary membership among European adults (N = 31,985). Specifically, it examines which values orient two age groups (middle age: 50-64 and old age: 65-79), as well as men and women toward a certain type of association (Social Awareness; Professional and Political; Education and Leisure; Religion). The sample of 31,985 comprises 60% of adults aged 50-64 and 40% aged 65-79; of which 56% are women and 44% men. The empirical estimation considers different levels of data aggregation: individual, national and welfare system, therefore multilevel analysis is used as an analytical strategy. Individual-level variables from the Integrated Values Survey (2005/09, 2010/14, and 2017/20) and national-level variables (Gini Index and Gross Domestic Product Per Capita) from the World Bank and Eurostat are used. The results indicate that traditional and self-expression values promote membership in voluntary organizations in general more than secular and survival values. However, there are differences according to the type of organization. Furthermore, values are found to moderate the effect of age and gender on voluntary membership.

A bacterial endosymbiont of the fungus Rhizopus microsporus drives phagocyte evasion and opportunistic virulence.

Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood. Here, we show that a clinical isolate of Rhizopus microsporus contains a Ralstonia pickettii bacterial endosymbiont required for virulence in both zebrafish and mice and that this endosymbiosis enables the secretion of factors that potently suppress growth of the soil amoeba Dictyostelium discoideum, as well as their ability to engulf and kill other microbes. As amoebas are natural environmental predators of both bacteria and fungi, we propose that this tri-kingdom interaction contributes to establishing endosymbiosis and the acquisition of anti-phagocyte activity. Importantly, we show that this activity also protects fungal spores from phagocytosis and clearance by human macrophages, and endosymbiont removal renders the fungal spores avirulent in vivo. Together, these findings describe a new role for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in animals and suggest a mechanism of virulence acquisition through environmental interactions with amoebas.

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.

Draft Genome Sequences of Clinical and Environmental Isolates of Aspergillus tamarii from Colombia.

Aspergillus is a very diverse genus of fungi that are common in the environment and can affect human health. Here, we report the draft genome sequences of two Colombian isolates of Aspergillus tamarii, an emerging pathogenic species. One isolate was obtained from an infected patient and the other from the environment in a hospital.

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.

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.

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.

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.

The complete mitochondrial genome of Xiphister atropurpureus (Perciformes: Stichaeidae).

Analysis of the marine black prickleback Xiphister atropurpureus Kittlitz using 76 bp paired-end Illumina sequences resulted in the assembly of its complete mitogenome. The mitogenome is 16,518 bp in length and contains an origin of light strand replication (OL), control region, 22 tRNA, 2 rRNA, and 13 protein-coding genes. Content and organization of the X. atropurpureus mitogenome is consistent with other teleost. Phylogenetic analysis of X. atropurpureus resolves it in a clade with another member of the Stichaeidae, Chirolophis japonicus Herzenstein.

Organellar genome analysis of the marine red alga Dasya binghamiae (Dasyaceae, Rhodophyta) reveals an uncharacteristic florideophyte mitogenome structure.

Analysis of the marine red algal species Dasya binghamiae A.J.K. Millar using paired-end 36 bp Illumina sequences resulted in the assembly of its complete mitochondrial and plastid genomes. The mitogenome is 26,052 bp in length and contains 46 genes, and the plastome is 177,213 bp with 228 genes. The plastid genome shows high gene synteny with previously published Florideophyceae; however, the mitogenome contains several multigene rearrangements. These organellar data confirm the placement of D. binghamiae in Dasya C. Agardh.

Economic Evaluation of Exercise-Based Cardiac Rehabilitation Programs for Chronic Heart Failure Patients in Colombia.

PURPOSE: Cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) has met with resistance from third-party payers in low- and middle-income countries because of lack of evidence regarding its cost-effectiveness. We aimed to provide information to help better inform this decision-making process. METHODS: Costs associated with a 12-week exercise-based rehabilitation program in Colombia for patients with CHF were estimated. We collected data on all medical resources used in ambulatory care and data on hospital costs incurred for treating patients with uncompensated CHF. A literature search to establish the hospitalization rates because of uncompensated CHF, death because of CHF, and potential decreases in these data because of the utilization of CR was conducted. We modeled incremental costs and effectiveness over a period of 5 years from the perspective of the third-party payer. RESULTS: All costs were converted from Colombian pesos to US dollars. For an exercise-based CR program of 12-week duration (36 sessions), costs ranged from US$265 to US$369 per patient. Monthly costs associated with ambulatory care of CHF averaged US$128 ± US$321 per patient, and hospitalization costs were US$3621 ± US$5 444 per event. Yearly hospitalization incidence rates with and without CR were 0.154 and 0.216, respectively. The incremental cost of CR would be US$998 per additional quality-adjusted life-year. Sensitivity analysis did not significantly change these results. CONCLUSIONS: Cardiac rehabilitation in patients with CHF in settings such as Colombia can be a cost-effective strategy, with minimal incremental costs and better quality of life, mainly because of decreased rates of hospitalization.

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.