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Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii (sensu stricto), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii's increased virulence and drug resistance.
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Genoma Bacteriano , Genômica , Infecções por Mycobacterium não Tuberculosas , Mycobacterium kansasii , Filogenia , Mycobacterium kansasii/genética , Mycobacterium kansasii/classificação , Mycobacterium kansasii/isolamento & purificação , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Animais , Virulência/genéticaRESUMO
Anterior cruciate ligament (ACL) instability poses a considerable challenge in traumatology and orthopedic medicine, demanding precise diagnostics for optimal treatment. The pivot-shift test, a pivotal assessment tool, relies on subjective interpretation, emphasizing the need for supplementary imaging. This study addresses this limitation by introducing a machine learning classification algorithm integrated into a mobile application, leveraging smartphones' built-in inertial sensors for dynamic rotational stability assessment during knee examinations. Orthopedic specialists conducted knee evaluations on a cohort of 52 subjects, yielding valuable insights. Quantitative analyses, employing the Intraclass Correlation Coefficient (ICC), demonstrated robust agreement in both intraobserver and interobserver assessments. Specifically, ICC values of 0.94 reflected strong concordance in the timing between maneuvers, while signal amplitude exhibited consistency, with the ICC ranging from 0.71 to 0.66. The introduced machine learning algorithms proved effective, accurately classifying 90% of cases exhibiting joint hypermobility. These quantifiable results underscore the algorithm's reliability in assessing knee stability. This study emphasizes the practicality and effectiveness of implementing machine learning algorithms within a mobile application, showcasing its potential as a valuable tool for categorizing signals captured by smartphone inertial sensors during the pivot-shift test.
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Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) is a disease of premature aging, characterized by airflow limitations in the lungs and systemic chronic inflammation. This systematic review aimed to provide a systematic overview of immunosenescence and inflammation in Chronic Obstructive Pulmonary Disease (COPD). Methods: The PubMed, Science Direct, Scopus, Cochrane Library, and Web of Science databases were searched for studies on markers of immunosenescence. Observational studies comparing patients with COPD to individuals without disease were evaluated, considering the following markers: inflammation and senescence in COPD, naïve, memory, and CD28null T cells, and telomere length in leukocytes. Results: A total of 15 studies were included, eight of which were rated as high quality. IL-6 production, telomere shortening, and the higher frequencies of CD28null T cells were more prominent findings in the COPD studies analyzed. Despite lung function severity being commonly investigated in the included studies, the importance of this clinical marker to immunosenescence remains inconclusive. Conclusions: The findings of this systematic review confirmed the presence of accelerated immunosenescence, in addition to systemic inflammation, in stable COPD patients. Further studies are necessary to more comprehensively evaluate the impact of immunosenescence on lung function in COPD.
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Thirty-five cladocerans species are recorded from La Española lagoon in the Orinoquia region of Colombia; all are new records for Meta Department and 10 for Colombia. With the addition of these new reports, the total number of cladocerans for Colombia and the Meta department is increased by 124 and 38 species, respectively. The cladoceran fauna from the surveyed area is represented mainly by widespread species, commonly found in the Neotropical regions, but local morphological data are scarce in the regional literature. Brief diagnostic description of 18 species of cladoceran fauna recorded of the Meta department-Colombia are provided together with illustrations of taxonomically significant appendages, morphological remarks, notes on the variability of some species, and their distribution.
Se registran treinta y cinco especies de cladóceros de la laguna La Española en la región de la Orinoquia de Colombia; todos ellos son nuevos registros para el Departamento del Meta y 10 para Colombia. Con la incorporación de estos nuevos reportes, el número total de cladóceros para Colombia y el departamento del Meta se incrementa en 124 y 38 especies respectivamente. La fauna de cladóceros del área estudiada está representada principalmente por especies de amplia distribución y que se encuentran comúnmente en las regiones Neotropicales, pero los datos morfológicos locales son escasos en la literatura regional. Se proporcionan breves descripciones diagnosticas de 18 especies registradas para la fauna de cladóceros del departamento del Meta-Colombia, junto con ilustraciones de apéndices taxonómicamente significativos, comentarios morfológicos, notas sobre la variabilidad de algunas especies y su distribución.
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A regulator based on a converter with step-down/up characteristics is discussed in this paper, which is suitable for processing energy from a lithium-ion battery pack, where the voltage fluctuates from above or below the nominal value. However, this regulator can also be used for applications such as unregulated line rectifiers and renewable energy sources, among others. The converter consists of a non-cascaded interconnection of boost and buck-boost converters such that part of the input energy is transferred directly to the output without reprocessing. Furthermore, it has a non-pulsating input current and a non-inverting output voltage, making it easier to feed the power to other devices. For control purposes, non-linear and linear converter models are derived. The transfer functions of the linear model are used to implement the regulator using a current-mode control scheme. Finally, experimental results for a nominal output voltage of 48 V at 500 W are obtained for the converter in open-loop and closed-loop tests.
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INTRODUCTION: Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by motor and / or vocal tics for more than 12 months. TS affects about 0.8% of pediatric patients and is associated with great functional impairment and psychological distress. The present study aims to list and compare the effectiveness of therapies used in children and young people with TS. METHODS: PubMed / MEDLINE, Cochrane Library, ScienceDirect, SciELO and Lilacs were used from September 2020 to April 2021 to search for randomized clinical trials with pharmacological, behavioral, physical or alternative interventions for tics in children and young people with ST. RESULTS: 13 clinical trials were included, of which six pharmacological, six behavioral and one of other conformation. The global score on the Yale Global Tic Severity Scale showed evidence in favor of Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT). Evidence from two studies suggests that antipsychotic medications improve tic scores. Evidence from other interventions has shown no conclusive benefit. CONCLUSIONS: The present study identified benefits with the use of antipsychotics. The study also found that HRT and CBIT showed improvement in reducing the severity of tics, in addition to not having any adverse effects. These therapies showed significant clinical improvement, but there is no comparison between the use of these isolated approaches in relation to their use associated with medications. In view of the different forms of therapy, further studies are needed to identify the effectiveness and the profile of adverse effects of these interventions.
INTRODUÇÃO: A Síndrome de Tourette (ST) é um distúrbio do neurodesenvolvimento caracterizado por tiques motores e/ou vocais por mais de 12 meses. A ST afeta cerca de 0,8% dos pacientes pediátricos e associa-se a grande comprometimento funcional e sofrimento psíquico. O presente estudo tem como objetivo listar e comparar a eficácia das terapias utilizadas em crianças e jovens com ST. MÉTODOS: PubMed/MEDLINE, Cochrane Library, ScienceDirect, SciELO e Lilacs foram usados desde setembro de 2020 até abril de 2021 para a busca de ensaios clínicos randomizados com intervenções farmacológicas, comportamentais, físicas ou alternativas para tiques em crianças e jovens com ST. RESULTADOS: 13 ensaios clínicos foram incluídos, dos quais seis farmacológicos, seis comportamentais e um de outra conformação. A pontuação global na Yale Global Tic Severity Scale, apresentou evidências a favor do Treinamento de Reversão de Hábito (TRH) e Intervenção Comportamental Abrangente para Tiques (ICAT). As evidências de dois estudos sugerem que medicamentos antipsicóticos melhoram os escores de tiques. Evidências de outras intervenções não mostraram nenhum benefício conclusivo. CONCLUSÕES: O presente estudo identificou benefícios com o uso do antipsicóticos. O estudo também identificou que a TRH e a ICAT apresentaram melhora na redução da gravidade dos tiques, além de não apresentarem efeitos adversos. Essas terapias mostraram importante melhora clínica, mas não há comparação entre o uso dessas abordagens isoladas em relação ao seu uso associado com medicamentos. Diante das diferentes formas de terapia, mais estudos são necessários para identificar a eficácia e o perfil de efeitos adversos dessas intervenções.
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Humanos , Criança , Adolescente , Transtornos de Tique/terapia , Terapia Comportamental , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/tratamento farmacológico , Placebos , Antipsicóticos/farmacologia , Resultado do Tratamento , Aripiprazol/farmacologiaRESUMO
In this paper, a high step-up boost converter with a non-isolated configuration is proposed. This configuration has a quadratic voltage gain, suitable for processing energy from alternative sources. It consists of two boost converters, including a transfer capacitor connected in a non-series power transfer structure between input and output. High power efficiencies are achieved with this arrangement. Additionally, the converter has a common ground and non-pulsating input current. Design conditions and power efficiency analysis are developed. Bilinear and linear models are derived for control purposes. Experimental verification with a laboratory prototype of 500 W is provided. The proposed configuration and similar quadratic configurations are compared experimentally using the same number of components to demonstrate the power efficiency improvement. The resulting power efficiency of the prototype was above 95% at nominal load.
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The mayflies are insects widely known as indicators of aquatic quality in freshwater systems, they are abundant and diverse in tropical streams. In this study, it was determined the influence of physical, chemical and bacteriological characteristics on the Ephemeroptera assembly in a period of low precipitation in the Ocoa river of Meta department. There were 5,332 nymphs belonging to 4 families, 10 genera and 3 species. Three new genera records and one species are presented for Meta: Cloeodes, Zelusia, Lumahyphes and Americabaetis alphus. The genera Camelobaetidius and Varipes were found associated with conditions of contamination by organic matter and water mineralization. Likewise, Americabaetis, Thraulodes, Lumahyphesand Tricorythodes were associated with contamination conditions, especially with nitrites and nitrates. Nanomis, Cloeodes and Zelusia showed greater sensitivity to the contamination condition and were related to high percentages of dissolved oxygen in the water and they were in the sampling stations of the upper part in the river. It is important to mention that there were not Ephemeroptera in most of the stations associated with the urban area. That reflects their high sensitivity to polluting conditions at low precipitation period.(AU)
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Animais , Ephemeroptera/química , Ephemeroptera/crescimento & desenvolvimento , Fenômenos QuímicosRESUMO
The mayflies are insects widely known as indicators of aquatic quality in freshwater systems, they are abundant and diverse in tropical streams. In this study, it was determined the influence of physical, chemical and bacteriological characteristics on the Ephemeroptera assembly in a period of low precipitation in the Ocoa river of Meta department. There were 5,332 nymphs belonging to 4 families, 10 genera and 3 species. Three new genera records and one species are presented for Meta: Cloeodes, Zelusia, Lumahyphes and Americabaetis alphus. The genera Camelobaetidius and Varipes were found associated with conditions of contamination by organic matter and water mineralization. Likewise, Americabaetis, Thraulodes, Lumahyphesand Tricorythodes were associated with contamination conditions, especially with nitrites and nitrates. Nanomis, Cloeodes and Zelusia showed greater sensitivity to the contamination condition and were related to high percentages of dissolved oxygen in the water and they were in the sampling stations of the upper part in the river. It is important to mention that there were not Ephemeroptera in most of the stations associated with the urban area. That reflects their high sensitivity to polluting conditions at low precipitation period.
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Animais , Ephemeroptera/crescimento & desenvolvimento , Ephemeroptera/química , Fenômenos QuímicosRESUMO
Abstract The mayflies are insects widely known as indicators of aquatic quality in freshwater systems, they are abundant and diverse in tropical streams. In this study, it was determined the influence of physical, chemical and bacteriological characteristics on the Ephemeroptera assembly in a period of low precipitation in the Ocoa river of Meta department. There were 5,332 nymphs belonging to 4 families, 10 genera and 3 species. Three new genera records and one species are presented for Meta: Cloeodes, Zelusia, Lumahyphes and Americabaetis alphus. The genera Camelobaetidius and Varipes were found associated with conditions of contamination by organic matter and water mineralization. Likewise, Americabaetis, Thraulodes, Lumahyphes and Tricorythodes were associated with contamination conditions, especially with nitrites and nitrates. Nanomis, Cloeodes and Zelusia showed greater sensitivity to the contamination condition and were related to high percentages of dissolved oxygen in the water and they were in the sampling stations of the upper part in the river. It is important to mention that there were not Ephemeroptera in most of the stations associated with the urban area. That reflects their high sensitivity to polluting conditions at low precipitation period.
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INTRODUCTION: Nontuberculous mycobacteria (NTM) species, as human pathogens, are increasing in the world, as is the difficulty of accurately identifying them. Differential diagnosis, especially between the M. tuberculosis complex and NTM species, and the characterization of NTM species is important. This study aimed to evaluate the performance of a molecular system based on multiplex real-time PCR with high-resolution melting (HRM) for the identification and differentiation of NTM species of clinical importance of an endemic area for tuberculosis in northeastern Brazil. METHODS: The technical protocol of the molecular system was based on multiplex real-time PCR-HRM, and evaluated the sensitivity and specificity of the detection of NTM species in mycobacterial clinical isolates from the studied region. The gold standard method was specific gene sequencing. RESULTS: The sensitivity and specificity of multiplex real-time PCR-HRM modified for differentiation between NTM and M. tuberculosis were 90% and 100%, respectively. The PCR-HRM sensitivities for the characterization of NTM species (M. kansasii, M. abscesses, M. avium, and M. fortuitum) were 94.59%, 80%, 57.14%, and 54%, respectively. CONCLUSIONS: The multiplex real-time PCR-HRM modified assay has the potential to rapidly and efficiently identify nontuberculous mycobacteria of clinical importance, which is crucial for immediate implementation of the appropriate therapy and thus avoiding complications and sequelae in patients.
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Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Tuberculose , Brasil , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium tuberculosis/genética , Micobactérias não Tuberculosas/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC), including Mycobacterium tuberculosis var. tuberculosis (MTB) and Mycobacterium tuberculosis var. africanum (MAF). While MTB is isolated worldwide, MAF is almost completely restricted to the African continent, and despite the historical proximity between Brazil and Africa during the slave trade, no case of TB being caused by MAF has been reported in Brazil to date. We hereby describe the first case of TB caused by MAF in Brazil comparing its genome against the published ones. A female patient who had never visited Africa presented with clinical symptoms typical of pulmonary TB. Based on 16S rRNA gene sequencing, the cultured isolate was identified as belonging to MTBC and partial sequence of the hsp65 gene was identical to that of MAF. This was confirmed by genotyping based on detection of Single Nucleotide Polymorphism (SNP), Region of Difference (RD) and spoligotyping. The isolate presented the Shared International Typing (SIT) 181. In the whole-genome comparison against MAF genomes available on published EMBL-EBI European Nucleotide Archive (ENA), the Brazilian genome (MAFBRA00707) was identified as belonging to Lineage 6 and clustered with isolates from The Gambia. This is the first report of the isolation of MAF from a patient from Brazil, without evidence of having any contact with an African index case.
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Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Brasil/epidemiologia , Genes Bacterianos , Genoma Bacteriano , Genótipo , Humanos , Epidemiologia Molecular , Tipagem Molecular , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 16S , Tuberculose Pulmonar/epidemiologiaRESUMO
Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.
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Antituberculosos/uso terapêutico , Pneumopatias/tratamento farmacológico , Pulmão/diagnóstico por imagem , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium kansasii/isolamento & purificação , Brasil/epidemiologia , Resistência Microbiana a Medicamentos , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/uso terapêutico , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Rifampina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.
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Peptídeos Catiônicos Antimicrobianos/farmacologia , Anuros/metabolismo , Hipocampo/efeitos dos fármacos , Infecções/tratamento farmacológico , Neurônios/efeitos dos fármacos , Sequência de Aminoácidos/genética , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Hipocampo/metabolismo , Infecções/induzido quimicamente , Infecções/genética , Infecções/microbiologia , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/genética , Neurônios/metabolismo , Nitritos/antagonistas & inibidores , Nitritos/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Abstract INTRODUCTION: Nontuberculous mycobacteria (NTM) species, as human pathogens, are increasing in the world, as is the difficulty of accurately identifying them. Differential diagnosis, especially between the M. tuberculosis complex and NTM species, and the characterization of NTM species is important. This study aimed to evaluate the performance of a molecular system based on multiplex real-time PCR with high-resolution melting (HRM) for the identification and differentiation of NTM species of clinical importance of an endemic area for tuberculosis in northeastern Brazil. METHODS: The technical protocol of the molecular system was based on multiplex real-time PCR-HRM, and evaluated the sensitivity and specificity of the detection of NTM species in mycobacterial clinical isolates from the studied region. The gold standard method was specific gene sequencing. RESULTS: The sensitivity and specificity of multiplex real-time PCR-HRM modified for differentiation between NTM and M. tuberculosis were 90% and 100%, respectively. The PCR-HRM sensitivities for the characterization of NTM species (M. kansasii, M. abscesses, M. avium, and M. fortuitum) were 94.59%, 80%, 57.14%, and 54%, respectively. CONCLUSIONS The multiplex real-time PCR-HRM modified assay has the potential to rapidly and efficiently identify nontuberculous mycobacteria of clinical importance, which is crucial for immediate implementation of the appropriate therapy and thus avoiding complications and sequelae in patients.
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Humanos , Tuberculose , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium tuberculosis/genética , Brasil , Reação em Cadeia da Polimerase em Tempo Real , Micobactérias não Tuberculosas/genéticaRESUMO
Twenty-one pulmonary sputum samples from nine Brazilian patients were analyzed by the PRA-hsp65 method for identification of Mycobacterium species and the results were compared by sequencing. We reported a mutation at the position 381, that generates a suppression cutting site in the BstEII enzyme, thus leading to a new PRA-hsp65 pattern for M. asiaticum identification.
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Infecções por Mycobacterium/microbiologia , Mycobacterium/classificação , Mutação Puntual , Brasil , DNA Bacteriano/genética , Humanos , Mycobacterium/genética , Mycobacterium/isolamento & purificação , Filogenia , Reação em Cadeia da Polimerase/métodos , Escarro/microbiologiaRESUMO
OBJECTIVES: Mycobacterium kansasii (M. kansasii) pulmonary infection can cause disease with clinical and radiological features similar to tuberculosis. Failure to treat M. kansasii infection is usually associated with resistance; to increase the chance of successful treatment it is important to identify the species and know the susceptibility profile. This study aimed to evaluate the antimycobacterial susceptibility profiles of M. kansasii isolates from Brazil. METHODS: Sixty-nine M. kansasii isolates from 69 patients were identified by partial sequencing of the hsp65 gene, and their susceptibility profiles were analysed by minimal inhibitory concentration (MIC) assays. RESULTS: From 69 isolates, 68 showed susceptibility to clarithromycin, amikacin, and moxifloxacin. Most strains showed high rates of resistance to trimethoprim-sulfamethoxazole and ciprofloxacin. Resistance to rifampicin and ethambutol was found in 12% and 25% of isolates, respectively. CONCLUSIONS: Worrying results were found regarding susceptibility to some drugs used as first-line agents in the treatment of diseases caused by M. kansasii.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium kansasii/efeitos dos fármacos , Proteínas de Bactérias/genética , Brasil , Chaperonina 60/genética , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Tuberculosis patients taking second line drugs such as ethionamide (ETH) have often experienced previous treatment failure and usually have a complex history of disease and treatment that can span decades. Mutations in the ETH activating enzyme, EthA, confer resistance through undescribed mechanisms. To explore the impact of EthA mutations on ETH resistance, data from a total of 160 ETHR isolates was analysed. The most frequently mutated positions are within regions that display sequence conservation with the active site of OTEMO, another FAD-containing NADH-binding Baeyer-Villiger monooxygenase (BVMO), or with the sugar binding site of galectin-4N. Additionally, to look at a possible role of EthR on ETH resistance we purified an EthR mutant identified in a clinical isolate, F110L, and found it to bind the ethA-ethR intergenic region with higher affinity than the wild type regulator in gel shift assays. The ability of cyclic di-GMP to enhance DNA binding is maintained in the EthR mutant. To our knowledge, this is the first ETH resistance study that combines sequence and resistance data of clinical isolates with functional and structural information.
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Antituberculosos/uso terapêutico , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Etionamida/uso terapêutico , Loci Gênicos , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Sítios de Ligação , DNA Bacteriano/isolamento & purificação , Genótipo , Humanos , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/isolamento & purificação , Oxirredutases/genética , Fenótipo , Ligação Proteica , Conformação Proteica , Proteínas Repressoras/genética , Relação Estrutura-Atividade , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.
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Genoma Bacteriano , Genótipo , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium kansasii/genética , Brasil , Gráficos por Computador , DNA Bacteriano , Genômica , Humanos , Mycobacterium kansasii/isolamento & purificação , Polimorfismo de Fragmento de RestriçãoRESUMO
Drug-resistant tuberculosis (DR-TB) poses a serious threat to tuberculosis (TB) control in Brazil and worldwide. The current study investigated factors associated with loss to follow-up and death in the course of treatment for DR-TB in a tertiary reference center in the city of Rio de Janeiro, Brazil. This was a retrospective cohort study of cases reported to the Information System on Special Treatments for Tuberculosis (SITETB) from January 1, 2012, to December 31, 2013. A total of 257 patients were reported to the SITETB and initiated treatment for DR-TB. Of this total, 139 (54.1%) achieved treatment success as the outcome, 54 (21%) were lost to follow-up, and 21 (8.2%) died. Following a multiple multinomial logistic regression analysis, the age bracket older than 50 years was the only protective factor against loss to follow-up, whereas less than eight years of schooling and reentry after loss to follow-up were considered risk factors. Reentry after loss to follow-up, relapse, and treatment failure appeared as risk factors. Our data reinforce the concept that loss to follow-up in drug-resistant tuberculosis is a serious public health problem, and that adequate follow-up of treatment is necessary in patients with this history and low schooling. A social support network for patients is also indispensable for avoiding unfavorable outcomes.
A tuberculose drogarresistente (TBDR) representa hoje uma grave ameaça aos avanços no controle da tuberculose (TB) no Brasil e no mundo. Neste estudo, investigam-se fatores associados ao abandono e ao óbito de casos em tratamento para TBDR, em um centro de referência terciária do Município do Rio de Janeiro, Brasil. Trata-se de um estudo de coorte retrospectiva, a partir dos casos notificados no Sistema de Informação de Tratamentos Especiais de Tuberculose (SITETB), no período de 1º de janeiro de 2012 a 31 de dezembro de 2013. Um total de 257 pacientes foi notificado no SITETB e iniciou o tratamento para TBDR. Desse total, 139 (54,1%) tiveram sucesso terapêutico como desfecho, 54 (21%) abandonaram o tratamento e 21 (8,2%) evoluíram para óbito. Após análise de regressão logística multinomial múltipla, a faixa etária acima de cinquenta anos foi observada como único fator de proteção ao abandono, ao passo que ter menos de oito anos de escolaridade e reingresso após abandono foram considerados como fatores de risco. Reingresso após abandono, recidiva e falência indicaram fatores de risco. Nossos dados reforçam a concepção de que o abandono do tratamento de tuberculose resistente é um sério problema de saúde pública, sendo necessário um adequado acompanhamento no tratamento de pacientes com esse histórico e com baixa escolaridade. Além disso, uma rede de apoio social ao paciente é imprescindível para que desfechos desfavoráveis sejam evitados.
La tuberculosis farmacorresistente (TBFR) representa hoy una grave amenaza para los avances en el control de la tuberculosis (TB) en Brasil y en el mundo. En este estudio, se investigan factores asociados al abandono y al óbito de casos en tratamiento para TBDR, dentro de un centro de referencia de carácter terciario del municipio de Río de Janeiro, Brasil. Se trata de un estudio de cohorte retrospectiva, a partir de los casos notificados en el Sistema de Información de Tratamientos Especiales de Tuberculosis (SITETB), durante el período del 1 de enero de 2012 al 31 de diciembre de 2013. Un total de 257 pacientes fue notificado en el SITETB y comenzó el tratamiento para TBDR. De ese total, 139 (un 54,1%) tuvieron éxito terapéutico como desenlace, 54 (un 21%) abandonaron el tratamiento y un 21 (8,2%) evolucionaron hacia óbito. Tras el análisis de regresión logística multinomial múltiple, la franja de edad por encima de cincuenta años se observó como el único factor de protección al abandono, al mismo tiempo que tener menos de ocho años de escolaridad y reingresar en el sistema educativo tras el abandono fueron considerados como factores de riesgo. Reingreso tras abandono, recidiva e insolvencia indicaron factores de riesgo. Nuestros datos refuerzan la concepción de que el abandono del tratamiento de tuberculosis resistente es un serio problema de salud pública, siendo necesario un adecuado acompañamiento en el tratamiento de pacientes con este historial y con baja escolaridad. Además, una red de apoyo social entorno al paciente es imprescindible para que los desenlaces desfavorables sean evitados.