RESUMO

Background and Aims: Acute respiratory failure (ARF) is the most frequent cause of cardiorespiratory arrest and subsequent death in children worldwide. There have been limited studies regarding ARF in high altitude settings. The aim of this study was to calculate mortality and describe associated factors for severity and mortality in children with ARF. Methods: The study was conducted within a prospective multicentric cohort that evaluated the natural history of pediatric ARF. For this analysis three primary outcomes were studied: mortality, invasive mechanical ventilation, and pediatric intensive care unit (PICU) length of stay. Eligible patients were children older than 1 month and younger than 18 years of age with respiratory difficulty at the time of admission. Patients who developed ARF were followed at the time of ARF, 48 h later, at the time of discharge, and at 30 and 60 days after discharge. It was conducted in the pediatric emergency, in-hospital, and critical-care services in three hospitals in Bogotá, Colombia, from April 2020 to June 2021. Results: Out of a total of 685 eligible patients, 296 developed ARF for a calculated incidence of ARF of 43.2%. Of the ARF group, 90 patients (30.4%) needed orotracheal intubation, for a mean of 9.57 days of ventilation (interquartile range = 3.00-11.5). Incidence of mortality was 6.1% (n = 18). The associated factors for mortality in ARF were a history of a neurologic comorbidity and a higher fraction of inspired oxygen at ARF diagnosis. For PICU length of stay, the associated factors were age between 2 and 5 years of age, exposure to smokers, and respiratory comorbidity. Finally, for mechanical ventilation, the risk factors were obesity and being unstable at admission. Conclusions: ARF is a common cause of morbidity and mortality in children. Understanding the factors associated with greater mortality and severity of ARF might allow earlier recognition and initiation of prompt treatment strategies.

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Introducción: la fractura de cadera en adultos mayores constituye un problema de salud importante, ya que está asociada a mayor morbilidad y mortalidad. Por esta razón, se han creado protocolos de ortogeriatría para su abordaje, los cuales reportan resultados favorables.Objetivo: evaluar los desenlaces adversos perioperatorios en adultos mayores con fractura de cadera antes y después de la implementación de un protocolo de evaluación geriátrica integral (EGI).Metodología: estudio de casos y controles realizado en 136 pacientes (casos: 43; controles: 93) >65 años con fractura de cadera que fueron atendidos en un hospital de referencia entre 2020 y 2021 (casos), y 2015 y 2017 (controles). Se determinaron diferencias entre grupos mediante un análisis bivariado usando las pruebas de chi cuadrado o exacta de Fisher en variables categóricas, y las pruebas t de student o de Wilcoxon de los rangos con signo en variables continuas según la distribución de los datos.Resultados: los desenlaces adversos perioperatorios ocurrieron en el 62,7% de los casos y el 84,0% de los controles (p=0,007; OR:0,32; IC95%:0,13-0,73). La mediana de duración de la estancia hospitalaria fue 10 y 17 días en los casos y controles, respectivamente (RIQ: 8-14; RIQ 11-26), mientras que el tiempo entre el ingreso a urgencias y la cirugía fue 7 días (RIQ:5-11) y 11 días (RIQ:8-17), respectivamente (p=0.002). Conclusiones: la implementación de la EGI redujo los desenlaces adversos por fractura de cadera, principal-mente la duración de la estancia hospitalaria y el tiempo entre el ingreso y la cirugía, donde se observaron diferencias estadísticamente significativas entre ambos grupos

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Introduction: Hip fracture in elderly patients is a major health concern, as it is associated with increased morbidity and mortality. For this reason, orthogeriatric protocols have been created to approach it, reporting favorable outcomes.Objective: To evaluate adverse perioperative outcomes in elderly patients with hip fractures before and after the implementation of a comprehensive geriatric assessment (CGA) protocol.Methodology: Case-control study performed on 136 patients (cases: 43; controls: 93) >65 years old with a hip fracture, who were treated at a referral hospital between 2020 and 2021 (cases) and 2015 and 2017 (controls). Differences between groups were determined through bivariate analysis using Fisher's chi-square or exact tests on categorical variables, and Student's t-test or Wilcoxon signed-rank test on continuous variables depending on the distribution of the data.Results: Adverse perioperative outcomes occurred in 62.7% of cases and 84.0% of controls (p=0.007; OR:0.32; 95%CI:0.13-0.73). The median length of hospital stay was 10 and 17 days in cases and controls, respectively (IQR: 8-14; IQR 11-26), while the time between ED admission and surgery was 7 days (IQR:5-11) and 11 days (IQR:8-17), respectively (p=0.002).Conclusions: The implementation of the CGA protocol reduced adverse outcomes associated with hip fracture, mainly the length of hospital stay and the time between admission and surgery, in which statistically significant differences were observed between both groups

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Cellular tRNAs appear today as a diverse population of informative macromolecules with conserved general elements ensuring essential common functions and different and distinctive features securing specific interactions and activities. Their differential expression and the variety of post-transcriptional modifications they are subject to, lead to the existence of complex repertoires of tRNA populations adjusted to defined cellular states. Despite the tRNA-coding genes redundancy in prokaryote and eukaryote genomes, it is surprising to note the absence of genes coding specific translational-active isoacceptors throughout the phylogeny. Through the analysis of different releases of tRNA databases, this review aims to provide a general summary about those "missing tRNA genes." This absence refers to both tRNAs that are not encoded in the genome, as well as others that show critical sequence variations that would prevent their activity as canonical translation adaptor molecules. Notably, while a group of genes are universally missing, others are absent in particular kingdoms. Functional information available allows to hypothesize that the exclusion of isodecoding molecules would be linked to: 1) reduce ambiguities of signals that define the specificity of the interactions in which the tRNAs are involved; 2) ensure the adaptation of the translational apparatus to the cellular state; 3) divert particular tRNA variants from ribosomal protein synthesis to other cellular functions. This leads to consider the "missing tRNA genes" as a source of putative non-canonical tRNA functions and to broaden the concept of adapter molecules in ribosomal-dependent protein synthesis.

RESUMO

Human serum albumin presents in its primary structure only one free cysteine (Cys34) which constitutes the most abundant thiol of plasma. An antioxidant role can be attributed to this thiol, which is located in domain I of the protein. Herein we expressed domain I as a secretion protein using the yeast Pichia pastoris. In the initial step of ammonium sulfate precipitation, a brown pigment co-precipitated with domain I. Three chromatographic methods were evaluated, aiming to purify domain I from the pigment and other contaminants. Purification was achieved by cation exchange chromatography. The protein behaved as a non-covalent dimer. The primary sequence of domain I and the possibility of reducing Cys34 to the thiol state while avoiding the reduction of internal disulfides were confirmed by mass spectrometry. The reactivity of the thiol towards the disulfide 5,5´-dithiobis(2-nitrobenzoate) was studied and compared to that of full-length albumin. A ~24-fold increase in the rate constant was observed for domain I with respect to the entire protein. These results open the door to further characterization of the Cys34 thiol and its oxidized derivatives.

Assuntos

Antioxidantes/química , Cisteína/genética , Albumina Sérica Humana/genética , Compostos de Sulfidrila/química , Cromatografia por Troca Iônica , Cisteína/química , Expressão Gênica/genética , Humanos , Domínios Proteicos/genética , Multimerização Proteica , Saccharomycetales/genética , Albumina Sérica Humana/química

RESUMO

BACKGROUND: During breast cancer progression, the epithelial to mesenchymal transition has been associated with metastasis and endocrine therapy resistance; however, the underlying mechanisms remain elusive. To gain insight into this process, we studied the transition undergone by MCF7-derived cells, which is driven by the constitutive nuclear expression of a MKL1 variant devoid of the actin-binding domain (MKL1 ΔN200). We characterized the adaptive changes that occur during the MKL1-induced cellular model and focused on regulation of translation machinery and metabolic adaptation. METHODS: We performed a genome-wide analysis at the transcriptional and translational level using ribosome profiling complemented with RNA-Seq and analyzed the expression of components of the translation machinery and enzymes involved in energy metabolism. NGS data were correlated with metabolomic measurements and quantification of specific mRNAs extracted from polysomes and western blots. RESULTS: Our results reveal the expression profiles of a luminal to basal-like state in accordance with an epithelial to mesenchymal transition. During the transition, the synthesis of ribosomal proteins and that of many translational factors was upregulated. This overexpression of the translational machinery appears to be regulated at the translational level. Our results indicate an increase of ribosome biogenesis and translation activity. We detected an extensive metabolic rewiring occurring in an already "Warburg-like" context, in which enzyme isoform switches and metabolic shunts indicate a crucial role of HIF-1α along with other master regulatory factors. Furthermore, we detected a decrease in the expression of enzymes involved in ribonucleotide synthesis from the pentose phosphate pathway. During this transition, cells increase in size, downregulate genes associated with proliferation, and strongly upregulate expression of cytoskeletal and extracellular matrix genes. CONCLUSIONS: Our study reveals multiple regulatory events associated with metabolic and translational machinery adaptation during an epithelial mesenchymal-like transition process. During this major cellular transition, cells achieve a new homeostatic state ensuring their survival. This work shows that ribosome profiling complemented with RNA-Seq is a powerful approach to unveil in-depth global adaptive cellular responses and the interconnection among regulatory circuits, which will be helpful for identification of new therapeutic targets.

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Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted and cell wall proteins interact with the host and play important roles in pathogenicity. These proteins are explored as candidate diagnostic markers, potential drug targets or vaccine antigens, and more recently special attention is being given to the role of their post-translational modifications. With the purpose of contributing to the proteomic and glycoproteomic characterization of this important pathogen, we performed a shotgun analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass spectrometry and a label-free spectral counting normalization approach for protein quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the most abundant proteins belong to the extracellular region or cell wall compartment, and that the functional categories with higher protein abundance factor were virulence, detoxification and adaptation, and cell wall and cell processes. We could identify a group of proteins consistently detected in previous studies, most of which were highly abundant proteins. In culture filtrate, 140 proteins were predicted to contain one of the three types of bacterial N-terminal signal peptides. Besides, various proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the type VII secretion system using nonclassical secretion signals, were also identified. O-glycosylation was identified in 46 proteins, many of them lipoproteins and cell wall associated proteins. Finally, we provide proteomic evidence for 33 novel O-glycosylated proteins, aiding to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. These findings are expected to collaborate with the research on pathogen derived biomarkers, virulence factors and vaccine candidates, and to provide clues to the understanding of the pathogenesis and survival strategies adopted by M. tuberculosis.

Assuntos

Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidade , Proteoma , Proteômica/métodos , Antígenos de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo , Vacinas Bacterianas , Parede Celular , Cromatografia Líquida , Glicosilação , Interações Hospedeiro-Patógeno , Proteínas de Membrana/metabolismo , Espectrometria de Massas em Tandem , Tuberculose/microbiologia , Virulência , Fatores de Virulência/metabolismo

RESUMO

In both prokaryotic and eukaryotic genomes, synonymous codons are unevenly used. Such differential usage of optimal or non-optimal codons has been suggested to play a role in the control of translation initiation and elongation, as well as at the level of transcription and mRNA stability. In the case of membrane proteins, codon usage has been proposed to assist in the establishment of a pause necessary for the correct targeting of the nascent chains to the translocon. By using as a model UreA, the Aspergillus nidulans urea transporter, we revealed that a pair of non-optimal codons encoding amino acids situated at the boundary between the N-terminus and the first transmembrane segment are necessary for proper biogenesis of the protein at 37°C. These codons presumably regulate the translation rate in a previously undescribed fashion, possibly contributing to the correct interaction of ureA-translating ribosome-nascent chain complexes with the signal recognition particle and/or other factors, while the polypeptide has not yet emerged from the ribosomal tunnel. Our results suggest that the presence of the pair of non-optimal codons would not be functionally important in all cellular conditions. Whether this mechanism would affect other proteins remains to be determined.

RESUMO

La estancia hospitalaria prolongada durante un episodio de exacerbación en Enfermedad Pulmonar Obstructiva Crónica representa una condición que aumenta el riesgo de complicaciones médicas asociadas. Objetivo: El objetivo de este estudio fue determinar los factores asociados a una estancia hospitalaria prolongada en exacerbaciones de Enfermedad Pulmonar Obstructiva Crónica, a través de un modelo de predicción. Materiales y métodos: En un estudio de tipo corte transversal recopilamos los datos de los registros médicos en un hospital localizado en la región oriente de Colombia, entre los años 2012-2014. Se realizó análisis descriptivo, bivariado y multivariado Resultados: Un total de 212 pacientes fueron incluidos en este estudio, 61.32% presentaron estancia hospitalaria prolongada. Encontramos asociación estadística significativa entre estancia hospitalaria prolongada y las variables independientes producto del análisis bivariado: disnea (OR: 2.87 p = 0.04), fiebre (OR: 2; p = 0.02), oxígeno hospitalario (OR: 2.34, p = 0.003), anticolinérgicos hospitalarios (OR: 2.91, p = 0.002), antibiótico hospitalario (OR: 2.25, p = 0.004), segmentados (OR: 1.02, p= 0.01) y linfocitos (OR: 0.95, p = 0.003). El modelo predictivo tenía un valor de p de 0.4950 en el análisis de bondad (prueba de Pearson) y un valor de p de 0.2689 en el test de bondad de ajuste (prueba de Hosmer-Lemeshow) indicando adecuado ajuste. Además, el modelo presentó un área bajo la curva de 0.6588. Conclusiones: Nuestro modelo de predicción incluyo las variables: edad, anticolinérgicos y segmentados, por su asociación significativa. Tiene adecuado ajuste y con un buen patrón de predicción.

Assuntos

Humanos , Doença Pulmonar Obstrutiva Crônica , Hospitais , Tempo de Internação

RESUMO

A prolonged hospital length of stay during an episode of exacerbation of chronic obstructive pulmonary disease is a condition that increases the risk of suffering associated medical complications. Objective: The objective of this study was to determine the factors associated with a prolonged hospital length of stay in exacerbations of chronic obstructive pulmonary disease through a prediction model. Materials and Methods: In a cross-sectional study we gathered the data of the medical records of a hospital located in the Eastern region of Colombia, between years 2012 and 2014. We carried out a descriptive, bivariate and multivariate analysis. Results: A total of 212 patients were included in this study. 61.32% showed a prolonged hospital length of stay. We found a significant statistical association between the prolonged hospital stay and the independent variables of the bivariate analysis: dyspnea (OR [Odds Ratio]: 2.87 p = 0.04), fever (OR: 2; p = 0.02), inpatient oxygen (OR: 2.34, p = 0.003), inpatient anticholinergics (OR: 2.91, p = 0.002), inpatient antibiotic (OR: 2.25, p= 0.004), segs (OR: 1.02, p= 0.01) and lymphocytes (OR: 0.95, p = 0.003). The predictive model had a p value of 0.4950 in the analysis of goodness (Pearson Test) and a p value of 0.2689 in the goodness of fit test (Hosmer-Lemeshow Test), indicating an adequate fit. Also, the model showed an area under the curve of 0.6588. Conclusions: Our prediction model included the following variables: age, anticholinergics and segs, for their significant association. It has an adequate fit and a good pattern of prediction.

Assuntos

Humanos , Doença Pulmonar Obstrutiva Crônica , Hospitais , Tempo de Internação

RESUMO

RESUMEN Introducción: La salud móvil es una forma económica de mejorar el control y seguimiento de los pacientes, y puede ayudar a optimizar la atención de un centro médico. Sin embargo, su potencial aún no ha sido completamente estudiado. Objetivo: Exponer los efectos de la utilización de la aplicación móvil VILLAHEALTH en el comportamiento y desempeño del personal de enfermería. Métodos: Observación sistemática de personal de salud en sus labores diarias. Se escogieron a ocho enfermeras que poseían un dispositivo móvil, y que estaban familiarizadas con la aplicación del sistema Android; la misma que logra almacenar estados, tratamientos e información básica del paciente, y también programa tareas con notificaciones que se muestran en el calendario del celular. Se midió y comparó los tiempos de respuesta con y sin la ayuda de la aplicación. Resultados: Con las notificaciones de la aplicación, el 77,08 por ciento de las veces, las tareas eran comenzadas antes de 5 minutos de su programación, frente al 25,00 por ciento sin su ayuda. La media de tiempo de respuesta con la aplicación fue de 105,18 (± 86,08) segundos, mientras que sin la aplicación fue de 616,72 (± 223,30) segundos. Conclusión: Con la aplicación VILLAHEALTH, los usuarios empezaron sus actividades en los cinco primeros minutos a partir del inicio establecido en comparación a los 10 minutos sin ella. Además, la aplicación ayudó al personal de enfermería a reducir sus tiempos de respuesta para tratar a los pacientes(AU)

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ABSTRACT Introduction: Mobile health is an inexpensive way to improve the control and monitoring of patients, and may help improve the service a medical center has. However, Its full potential still hasn't been studied. Objective: To show the results of the infirmary personnel's behaviour when using the mobile application VILLAHEALTH in their professional performance. Methods: Systematic observation of health personnel in their daily work. Eight nurses were selected who owned a smartphone with Internet access and were familiarized with the Android application, which stores the states, treatments and basic patient information, and programs tasks with notifications which are displayed on the calendar. The response times with and without the help of the application were measured and compared. Results: With the application notifications, 77,08 percent of the time the tasks were started within 5 minutes of programming, compared to 25,00 percent without its help. The average response time with the application was 105,18 (± 86,08) seconds, while without it was 616,72 (± 223,30) seconds. Conclusion: Using the VILLAHEALTH app, users started their activities within the first five minutes, compared to the 10 minutes without using it. In addition, the app helped nurses reduce response times when treating patients(AU)

Assuntos

Humanos , Telemedicina/métodos , Aplicativos Móveis/tendências , Smartphone , Recursos Humanos de Enfermagem/ética

RESUMO

Haemonchus contortus is one of the most important parasite nematodes of small ruminants around the world and causes great economic losses in livestock production. Control of gastrointestinal nematode infections, like haemonchosis, relies mainly on anthelmintic drugs, but its excessive and inappropriate use has caused serious drug resistance issues in many countries, including Uruguay, where sheep production occupies an important place in the country's economy. Benzimidazole (BZ) anthelmintics have been used for decades to treat sheep against H. contortus infection and resistance to this anthelmintic group has been widely described. Molecularly, BZ resistance in H. contortus has been correlated with single nucleotide polymorphisms (SNPs) of the ß-tubulin isotype 1 gene at codon 200 and 167 (both TTC to TAC, F167Y and F200Y) and at codon 198 (GAA to GCA, E198A).The aim of this work was to explore the presence of these tubulin SNPs in H. contortus adult worms recovered from sheep abomasa from a slaughterhouse in Uruguay. The mean resistant allelic frequencies at positions F167Y and F200Y were 20.25 and 47.45%, respectively, for worms recovered from naturally infected sheep slaughtered in 2013, while those that were slaughtered in 2014 presented only F200Y SNP with a frequency of 86.89%. Also H. contortus Kirby adult worms (anthelmintic- susceptible McMaster isolate), recovered from artificially infected sheep, were analyzed as reference for comparative purposes This analysis showed susceptible genotype at 167 and 198 position, and a low level of the resistance allele at the 200 position (3.66%). This is the first study for the presence of SNPs in the isotype-1 ß-tubulin gene of H. contortus populations in Uruguay, which is consistent with the previous epidemiological studies carried out through the method of fecal egg count reduction test (FECRT), thus confirming the serious resistance levels to BZ anthelmintics also in this country.

Assuntos

Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Resistência a Medicamentos , Hemoncose/veterinária , Haemonchus/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Doenças dos Ovinos/epidemiologia , Matadouros , Alelos , Animais , Frequência do Gene , Genótipo , Hemoncose/epidemiologia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Ovinos/parasitologia , Doenças dos Ovinos/parasitologia , Tubulina (Proteína)/genética , Uruguai/epidemiologia

RESUMO

Microtubules are non-covalent cylindrical polymers formed by alpha- and beta-tubulin heterodimer units, crucial for cell division, intracellular transport, motility and differentiation. This makes them very attractive pharmacological targets exploited to develop different drugs such as anthelmintics, antifungals, and antineoplastics. In this work, in order to establish an in vitro target-based screen to integrate to the search for new anthelmintics, we explored the extraction of native assembly-competent tubulin from two helminth parasites: Mesocestoides vogae tetrathyridia (syn. corti, Cestoda: Cyclophyllidea), a useful cestode biological model, and Haemonchus contortus, a sheep gastrointestinal nematode of interest in livestock production. For this purpose, a novel tubulin affinity chromatography procedure was employed, based on the binding capacity of TOG (Tumor Overexpressed Gene) domain from MAPs (microtubule-associated proteins). The TOG domain of the protein Stu2 from Saccharomyces cerevisiae fused to GST (glutathione S- transferase) were produced in E. coli, and the immobilized recombinant proteins allowed for native tubulin extraction from parasites. The binding capacity of TOG1 affinity column (3.6%) was estimated using commercial porcine brain tubulin. A total amount of up to 126 µg of M. vogae tubulin was purified, whereas H. contortus tubulin co-eluted with glutamate dehydrogenase enzyme. The identity of tubulins was confirmed by western blotting and mass spectrometry. The abundance of tubulin estimated in M. vogae was 10% soluble extract, which probably could explain differences observed between tubulin purification results of both helminth parasites.

Assuntos

Cromatografia de Afinidade/métodos , Haemonchus/química , Mesocestoides/química , Proteínas Associadas aos Microtúbulos/metabolismo , Tubulina (Proteína)/isolamento & purificação , Sequência de Aminoácidos , Animais , Infecções por Cestoides/parasitologia , Escherichia coli/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Hemoncose/parasitologia , Hemoncose/veterinária , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ovinos , Doenças dos Ovinos/parasitologia , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Suínos , Tubulina (Proteína)/química , Tubulina (Proteína)/genética

RESUMO

Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.

RESUMO

Objetivo: Determinar las variables relacionadas con el desarrollo de secuelas fibrocavitarias torácicas en pacientes con antecedente de tuberculosis pulmonar en Santander. Métodos: Cohorte retrospectiva de 141 pacientes con diagnóstico previo de tuberculosis, captados mediante muestreo no probabilístico de casos consecutivos en consulta de neumología (Hospital Universitario de Santander). Se realizó un análisis descriptivo, bivariado y multivariado a las variables recolectadas de las historias clínicas. Resultados: El 66% de los pacientes pertenecían al sexo masculino, con una edad promedio de 52 ± 16,91 años, evidenciando un tiempo promedio desde el contagio hasta el momento de la captación de 69 meses y un antecedente de tabaquismo del 46%. El 68% referían tos y se realizó fibrobroncoscopia al 41%. El 89% mostraron algún tipo de secuelas, distribuidas así: Torácicas parenquimatosas 88%, Pleurales 30%, Vías respiratorias 45%, Mediastinales 38% y Vasculares 5%. Fueron variables asociadas a la presencia de alguna secuela la edad del paciente; el tiempo mayor a 17 meses desde el diagnóstico de tuberculosis; la edad de diagnóstico de tuberculosis; la confirmación diagnóstica de tuberculosis por fibrobroncoscopia y síntomas como disnea, cianosis y tos. Discusión: El presente estudio estableció la prevalencia de secuelas de tuberculosis en el 88,65% de los sujetos con tuberculosis curada en Bucaramanga, Santander, Colombia. Es el primer estudio en la región en el que se evaluaron factores asociados con el desarrollo de secuelas de tuberculosis, encontrando como factor importante el uso de fibrobroncoscopia como método diagnóstico.

Assuntos

Doenças Respiratórias , Tuberculose Pulmonar , Bronquiectasia

RESUMO

Objective: To determine the variables associated with the development of thoracic fibrocavitary sequelae in patients with a history of pulmonary tuberculosis in Santander. Methods: A retrospective cohort of 141 patients previously diagnosed with tuberculosis, recruited using non-probability consecutive sampling at pneumology consultations (Hospital Universitario de Santander). A descriptive, bivariate and multivariate analysis was performed with all the variables collected from the medical records. Results: Sixty-six percent of the patients were males, with an average age of 52+/-16.91 years, evidencing an average time span of 69 months from the moment of the infection to the moment they were recruited, and a history of tobacco use of 46%. Sixty-eight percent stated they had cough and a fibrobronchoscopy was performed in 41%. Eighty-nine percent exhibited some type of sequelae, classified as follows: Parenchymal thoracic 88%, pleural 30%, respiratory tract 45%, mediastinal 38% and vascular 5%. The variables associated with the presence of a sequela were the age of the patient; a period of time exceeding 17 months since the moment of the tuberculosis diagnosis; the age of diagnosis; the diagnostic confirmation of tuberculosis by fibrobronchoscopy and symptoms such as dyspnea, cyanosis and cough. Discussion: This study establishes the incidence of tuberculosis sequelae in 88.65% of the subjects with tuberculosis treated in Bucaramanga, Santander, Colombia. It is the first study in the region evaluating the factors associated with the development of tuberculosis sequelae, in which the use of fibrobronchoscopies as a diagnostic method was found to be an important factor.

Assuntos

Doenças Respiratórias , Tuberculose Pulmonar , Bronquiectasia

RESUMO

Bovine Respiratory Disease is the most costly disease that affects beef and dairy cattle industry. Its etiology is multifactorial, arising from predisposing environmental stress conditions as well as the action of several different respiratory pathogens. This situation has hindered the development of effective control strategies. Although different type of vaccines are available, many currently marketed vaccines are based on inactivated cultures of the main viral and bacterial agents involved in this pathology. The molecular composition of commercial veterinary vaccines is a critical issue. The present work aims to define at the proteomic level the most relevant valence of a line of commercial respiratory vaccines widely used in Central and South America. Since Mannheimia haemolytica is responsible for most of the disease associated morbid-mortality, we focused on the main proteins secreted by this pathogen, in particular Leukotoxin A, its main virulence factor. By Western blot analysis and mass spectrometry, Leukotoxin A was identified as a major component of M. haemolytica culture supernatants. We also identified other ten M. haemolytica proteins, including outer membrane proteins, periplasmic transmembrane solute transporters and iron binding proteins, which are relevant to achieve protective immunity against the pathogen. This work allowed a detailed molecular characterization of this vaccine component, providing evidence of its quality and efficacy. Furthermore, our results contributed to the identification of several proteins of interest as subunit vaccine candidates.

RESUMO

Las características biológicas del bacilo mycobacterium tuberculosis le permiten afectar casi cualquier tejido. Al ser la tuberculosis pulmonar la entidad más frecuente, se presenta la posibilidad de diseminación de la enfermedad a nivel torácico, lo que genera la aparición de secuelas que pueden afectar los órganos vitales de la caja torácica, tales como la vía aérea, el parénquima pulmonar, el sistema vascular pulmonar, el espacio pleural y la región mediastinal. Esto genera, además, la manifestación de trastornos funcionales que afectan directamente el pronóstico y la calidad de vida de los pacientes. La presente revisión trata de las secuelas torácicas encontradas en pacientes con antecedente de tuberculosis pulmonar. Estas se clasificaron así: secuelas de la vía aérea, secuelas parenquimatosas, secuelas pleurales, secuelas mediastinales, secuelas vasculares y secuelas funcionales.

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Because of its biologic characteristics, the Mycobacterium tuberculosis can affect any tissue of the human body. Since the lungs are the most frequently affected organs, it is common the dissemination of the infection in the thorax with the development of sequelae in the pulmonary parenchyma, the airways, the vascular pulmonary system, the pleural space and the mediastinum. The sequelae lead to functional disturbances with a direct effect on the prognosis and the quality of life of the patients. This is a review of the thoracic sequelae in patients with a history of pulmonary tuberculosis. The sequelae were classifed as airways, parenchymal, pleural, mediastinal, vascular and functional sequelae.

Assuntos

Tuberculose , Pneumopatias

RESUMO

Silent mutations are being intensively studied. We previously showed that the estrogen receptor alpha Ala87's synonymous polymorphism affects its functional properties. Whereas a link has been clearly established between the effect of silent mutations, tRNA abundance and protein folding in prokaryotes, this connection remains controversial in eukaryotic systems. Although a synonymous polymorphism can affect mRNA structure or the interaction with specific ligands, it seems that the relative frequencies of isoacceptor tRNAs could play a key role in the protein-folding process, possibly through modulation of translation kinetics. Conformational changes could be subtle but enough to cause alterations in solubility, proteolysis profiles, functional parameters or intracellular targeting. Interestingly, recent advances describe dramatic changes in the tRNA population associated with proliferation, differentiation or response to chemical, physical or biological stress. In addition, several reports reveal changes in tRNAs' posttranscriptional modifications in different physiological or pathological conditions. In consequence, since changes in the cell state imply quantitative and/or qualitative changes in the tRNA pool, they could increase the likelihood of protein conformational variants, related to a particular codon usage during translation, with consequences of diverse significance. These observations emphasize the importance of genetic code flexibility in the co-translational protein-folding process.

RESUMO

Estrogen receptor α (ERα) exerts regulatory actions through genomic mechanisms. In the classical pathway, ligand-activated ERα binds directly to DNA through estrogen response elements (ERE) located in the promoter of target genes. ERα can also exert indirect regulation of transcription via protein-protein interaction with other transcription factors such as AP-1.S everal ERα synonymous polymorphisms have been identified and efforts to understand their implications have been made. Nevertheless effects of synonymous polymorphisms are still neglected. This chapter focuses on the experimental procedure employed in order to characterize the transcriptional activity of a synonymous polymorphism of the ERα (rs746432) called Alanine 87 (Ala87). Activity of both WT and Ala87 ERα isoforms on transcriptional pathways can be analyzed in transiently transfected cells using different reporter constructs. ERα efficiency on the classical genomic pathway can be analyzed by determining its transactivation activity on an ERE-driven thymidine kinase (TK) promoter controlling the expression of the luciferase reporter gene. Transcriptional activity through the indirect genomic pathway can be analyzed by employing an AP-1 DNA response element-driven promoter also controlling the expression of luciferase reporter gene.

Assuntos

Receptor alfa de Estrogênio/metabolismo , Mutação , Elementos de Resposta , Timidina Quinase/genética , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional , Alanina , Receptor alfa de Estrogênio/genética , Regulação da Expressão Gênica , Genes Reporter , Células HeLa , Células Hep G2 , Humanos , Luciferases/genética , Luciferases/metabolismo , Ligação Proteica , Transcrição Gênica , Transfecção , Fluxo de Trabalho

RESUMO

Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system, with a prevalence of about 1:3000 people. Cystic fibrosis is caused by mutations in CFTR gene, which lead to a defective function of the chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Up-to-date, more than 1900 mutations have been reported in CFTR. However for an important proportion of them, their functional effects and the relation to disease are still not understood. Many of these mutations are silent (or synonymous), namely they do not alter the encoded amino acid. These synonymous mutations have been considered as neutral to protein function. However, more recent evidence in bacterial and human proteins has put this concept under revision. With the aim of understanding possible functional effects of synonymous mutations in CFTR, we analyzed human and primates CFTR codon usage and divergence patterns. We report the presence of regions enriched in rare and frequent codons. This spatial pattern of codon preferences is conserved in primates, but this cannot be explained by sequence conservation alone. In sum, the results presented herein suggest a functional implication of these regions of the gene that may be maintained by purifying selection acting to preserve a particular codon usage pattern along the sequence. Overall these results support the idea that several synonymous mutations in CFTR may have functional importance, and could be involved in the disease.

Assuntos

Códon , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Evolução Molecular , Modelos Genéticos , Mutação , Primatas/genética , Animais , Humanos